एम्फ़ैटेमिन

विकी से
नेविगेशन पर जाएं खोजने के लिए कूदो

साँचा: संक्षिप्त विवरण टेम्पलेट: बॉट टेम्पलेट: के बारे में टेम्पलेट: पुनर्निर्देशन टेम्पलेट: पीपी-अर्द्ध indef टेम्प्लेट: डमी तिथियों का उपयोग करें Template:Infobox drug

एम्फ़ैटेमिन[नोट 1] (contracted from alpha-mएथिलphenethylअमाइन) एक है केंद्रीय तंत्रिका तंत्र (सीएनएस) उत्तेजक पदार्थ marketed under the brand name Evekeoबीच में, दूसरों. It is used in the treatment of ध्यान घाटे hyperactivity विकार (ADHD), narcolepsy, तथा मोटापा. Amphetamine was discovered in 1887 and exists as two एनंटीओमर:[नोट 2] levoamphetamine तथा dextroamphetamine. एम्फ़ैटेमिन properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers, levoamphetamine and dextroamphetamine, in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer तथा cognitive enhancer, and recreationally as an कामोद्दीपक तथा euphoriant. यह एक है डॉक्टर की पर्चे की दवा in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with मनोरंजन के लिए.[sources 1]

The first amphetamine pharmaceutical was Benzedrine, a brand which was used to treat a variety of conditions. Currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall,[नोट 3] dextroamphetamine, or the inactive प्रोड्रग lisdexamfetamine. Amphetamine increases मोनोअमाइन तथा excitatory neurotransmission in the brain, with its most pronounced effects targeting the norepinephrine तथा डोपामाइन न्यूरोट्रांसमीटर सिस्टम.[sources 2]

At therapeutic doses, amphetamine causes emotional and cognitive effects such as उत्साह, change in सेक्स के लिए इच्छा, बढ़ा हुआ wakefulness, and improved संज्ञानात्मक नियंत्रण. It induces physical effects such as improved reaction time, fatigue resistance, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown. लत is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. Very high doses can result in मनोविकृति (जैसे, भ्रम तथा उन्माद) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects.[sources 3]

Amphetamine belongs to the phenethylamine class. It is also the parent compound of its own structural class, the substituted amphetamines,[नोट 4] which includes prominent substances such as bupropion, cathinone, एमडीएमए, तथा methamphetamine. As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring trace amine neuromodulators, specifically phenethylamine तथा खाका: nowrap, both of which are produced within the human body. Phenethylamine is the parent compound of amphetamine, while खाका: nowrap एक positional isomer of amphetamine that differs only in the placement of the मिथाइल समूह.[sources 4]

साँचा: TOC की सीमा

का उपयोग करता है

चिकित्सा

Amphetamine is used to treat ध्यान घाटे hyperactivity विकार (ADHD), narcolepsy (a sleep disorder), and मोटापा, and is sometimes prescribed खाका: nowrap for its past medical indications, particularly for अवसाद तथा पुराने दर्द.[32][16][33] Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal डोपामाइन प्रणाली development or nerve damage,[34][35] but, in humans with ADHD, pharmaceutical amphetamines, at therapeutic dosages, appear to improve brain development and nerve growth.[36][37][38] की समीक्षा चुम्बकीय अनुनाद इमेजिंग (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right पूंछवाला नाभिक का बेसल गैंग्लिया.[36][37][38]

Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.[25][39][40] Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety.[25][39] Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing जीवन की गुणवत्ता and academic achievement, and producing improvements in a large number of functional outcomes[नोट 5] across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function.[25][40] One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.[39] Another review indicated that, based upon the longest अनुवर्ती अध्ययन conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a पदार्थ उपयोग विकार as an adult.[25]

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's न्यूरोट्रांसमीटर सिस्टम;[41] these functional impairments involve impaired डोपामाइन neurotransmission in the mesocorticolimbic projection तथा norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus को प्रीफ्रंटल कॉर्टेक्स.[41] Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems.[7][41][42] Approximately 80% of those who use these stimulants see improvements in ADHD symptoms.[43] Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans.[44][45] प्रवेश कोक्रेन समीक्षा[नोट 6] on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse साइड इफेक्ट.[47][48] A Cochrane review on the treatment of ADHD in children with tic disorders जैसे टॉरेट सिंड्रोम indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.[49]

Enhancing performance

Cognitive performance

2015 में, एक व्यवस्थित समीक्षा और एक मेटा-विश्लेषण of high quality क्लिनिकल परीक्षण found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including कार्य स्मृति, long-term प्रासंगिक स्मृति, निरोधात्मक नियंत्रण, and some aspects of ध्यान, in normal healthy adults;[50][51] these cognition-enhancing effects of amphetamine are known to be partially mediated through the अप्रत्यक्ष सक्रियता दोनों की dopamine receptor D1 तथा adrenoceptor α2 में प्रीफ्रंटल कॉर्टेक्स.[7][50] A systematic review from 2014 found that low doses of amphetamine also improve स्मृति समेकन, in turn leading to improved recall of information.[52] Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals.[7][53] Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase कामोत्तेजना (wakefulness), in turn promoting goal-directed behavior.[7][54][55] Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid.[7][55][56] Based upon studies of self-reported illicit stimulant use, खाका: nowrap of college students use बँट ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs.[57][58][59] However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.[7][55]

Physical performance

Amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects, such as increased endurance and alertness;[8][21] however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies.[60][61] In healthy people at oral therapeutic doses, amphetamine has been shown to increase मांसपेशियों की ताकत, acceleration, athletic performance in anaerobic conditions, तथा सहनशीलता (i.e., it delays the onset of थकान), while improving प्रतिक्रिया समय.[8][62][63] Amphetamine improves endurance and reaction time primarily through reuptake inhibition तथा जारी of dopamine in the central nervous system.[62][63][64] Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch", allowing the core temperature limit to increase in order to access a reserve capacity that is normally off-limits.[63][65][66] At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance;[8][62] however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown तथा elevated body temperature.[9][62]

मतभेद

साँचा: देखिये के अनुसार International Programme on Chemical Safety (IPCS) and the United States Food and Drug Administration (USFDA),[नोट 7] amphetamine is contraindicated in people with a history of नशीली दवाओं के दुरुपयोग,[नोट 8] हृदय रोग, गंभीर आंदोलन, or severe anxiety.[16][9][68] It is also contraindicated in individuals with advanced धमनीकाठिन्य (hardening of the arteries), आंख का रोग (increased eye pressure), अतिगलग्रंथिता (excessive production of thyroid hormone), or moderate to severe अतिरक्तदाब.[16][9][68] These agencies indicate that people who have experienced एलर्जी to other stimulants or who are taking मोनोमाइन ऑक्सीडेज इनहिबिटर (MAOIs) should not take amphetamine,[16][9][68] although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented.[69][70] These agencies also state that anyone with आहार क्रिया विकार, द्विध्रुवी विकार, depression, hypertension, liver or kidney problems, उन्माद, मनोविकृति, Raynaud's phenomenon, बरामदगी, थाइरोइड समस्या का, ticsया, टॉरेट सिंड्रोम should monitor their symptoms while taking amphetamine.[9][68] Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus.[68] Amphetamine has also been shown to pass into breast milk, so the IPCS and the USFDA advise mothers to avoid breastfeeding when using it.[9][68] Due to the potential for reversible growth impairments,[नोट 9] the USFDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical.[9]

प्रतिकूल प्रभाव

प्रवेश adverse side effects of amphetamine are many and varied, and the amount of amphetamine used is the primary factor in determining the likelihood and severity of adverse effects.[9][21] Amphetamine products such as Adderall, Dexedrine, and their generic equivalents are currently approved by the USFDA for long-term therapeutic use.[17][9] मनोरंजन के लिए of amphetamine generally involves much larger doses, which have a greater risk of serious adverse drug effects than dosages used for therapeutic purposes.[21]

भौतिक

संचार प्रणाली side effects can include अतिरक्तदाब or हाइपोटेंशन एक से vasovagal response, Raynaud's phenomenon (reduced blood flow to the hands and feet), and क्षिप्रहृदयता (increased heart rate).[9][21][71] Sexual side effects in males may include सीधा होने के लायक़ रोग, frequent erections, or prolonged erections.[9] Gastrointestinal side effects may include पेट में दर्द, कब्ज, दस्त, तथा मतली.[32][9][72] Other potential physical side effects include भूख में कमी, धुंधली दृष्टि, शुष्क मुँह, excessive grinding of the teeth, nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold, tics (a type of movement disorder), and वजन घटना.[sources 5] Dangerous physical side effects are rare at typical pharmaceutical doses.[21]

Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths.[21] In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident.[21] Amphetamine also induces संकुचन in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating.[21] This effect can be useful in treating bed wetting तथा loss of bladder control.[21] The effects of amphetamine on the gastrointestinal tract are unpredictable.[21] If intestinal activity is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system);[21] however, amphetamine may increase motility when the कोमल मांसपेशियाँ of the tract is relaxed.[21] Amphetamine also has a slight एनाल्जेसिक effect and can enhance the pain relieving effects of नशीले पदार्थों.[32][21]

USFDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (अचानक मौत, दिल का दौरा, तथा आघात) and the medical use of amphetamine or other ADHD stimulants.[sources 6] However, amphetamine pharmaceuticals are contraindicated व्यक्तियों में हृदय रोग.[sources 7]

मनोवैज्ञानिक

At normal therapeutic doses, the most common psychological side effects of amphetamine include increased सजगता, apprehension, एकाग्रता, initiative, आत्मविश्वास and sociability, mood swings (elated mood followed by mildly उदास मन), अनिद्रा or wakefulness, and decreased sense of fatigue.[9][21] Less common side effects include चिंता, change in लीबीदो, grandiosity, चिड़चिड़ापन, repetitive or जुनूनी behaviors, and restlessness;[sources 8] these effects depend on the user's personality and current mental state.[21] Amphetamine psychosis (जैसे, भ्रम तथा उन्माद) can occur in heavy users.[9][22][23] Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy.[9][23][24] According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility.[9]

Amphetamine has also been shown to produce a वातानुकूलित स्थान वरीयता in humans taking therapeutic doses,[47][79] meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.[79][80]

Reinforcement disorders

लत

Template:Addiction glossary Template:Transcription factor glossary Template:Psychostimulant addiction लत is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses;[25][26][27] in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing पदार्थ का उपयोग विकार as an adult.[25] Template:If pagename Pathological overactivation of the मेसोलींबिक मार्गतक dopamine pathway that connects the उदर तेग्मेंतल क्षेत्र को केन्द्रीय अकम्बन्स, plays a central role in amphetamine addiction.[81][82] Individuals who frequently self-administer high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increase the level of accumbal ΔFosB, a "molecular switch" and "master control protein" for addiction.[83][84][85] Once nucleus accumbens ΔFosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression.[84][86] While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction.[87][88] Sustained aerobic exercise on a regular basis also appears to be an effective treatment for amphetamine addiction;[sources 9] exercise therapy improves नैदानिक treatment outcomes and may be used as an adjunct therapy with behavioral therapies for addiction.[87][89]

Biomolecular mechanisms

Chronic use of amphetamine at excessive doses causes alterations in जीन की अभिव्यक्ति में mesocorticolimbic projection, which arise through ट्रांस्क्रिप्शनल तथा epigenetic mechanisms.[85][90][91] सबसे महत्वपूर्ण प्रतिलेखन के कारक[नोट 10] that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), शिविर response element binding protein (CREB), और nuclear factor-kappa B (NF-κB).[85] ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB overexpression (i.e., an abnormally high level of gene expression which produces a pronounced gene-related फेनोटाइपमें) D1-type medium spiny neurons में केन्द्रीय अकम्बन्स is necessary and sufficient[नोट 11] for many of the neural adaptations and regulates multiple behavioral effects (e.g., reward sensitization and escalating drug आत्म प्रशासन) involved in addiction.[83][84][85] Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression.[83][84] It has been implicated in addictions to शराब, cannabinoids, कोकीन, methylphenidate, निकोटीन, नशीले पदार्थों, phencyclidine, propofol, तथा substituted amphetamines, दूसरों के बीच.[sources 10]

ΔJunD, a transcription factor, and G9aतक histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression.[83][85][95] Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[85] Similarly, accumbal G9a hyperexpression results in markedly increased histone 3 lysine अवशिष्ट 9 dimethylation (H3K9me2) and blocks the induction of ΔFosB-mediated तंत्रिका तथा behavioral plasticity by chronic drug use,[sources 11] which occurs via H3K9me2-mediated दमन of प्रतिलेखन के कारक for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g., CDK5).[85][95][96] ΔFosB also plays an important role in regulating behavioral responses to प्राकृतिक पुरस्कार, such as palatable food, sex, and exercise.[86][85][99] Since both natural rewards and addictive drugs induce the expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction.[86][85] Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use.[86][100][101] These sexual addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.[86][99]

The effects of amphetamine on gene regulation are both dose- and route-dependent.[91] Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses.[91] The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor.[91] This suggests that medical use of amphetamine does not significantly affect gene regulation.[91]

औषधीय उपचार

टेम्पलेट: आगे साँचा: के रूप में there is no effective pharmacotherapy for amphetamine addiction.[102][103][104] Reviews from 2015 and 2016 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions;[20][105] तथापि, साँचा: के रूप में the only compounds which are known to function as TAAR1-selective agonists are experimental drugs.[20][105] Amphetamine addiction is largely mediated through increased activation of डोपामाइन रिसेप्टर्स तथा खाका: nowrap NMDA receptors[नोट 12] in the nucleus accumbens;[82] magnesium ions inhibit NMDA receptors by blocking the receptor कैल्शियम चैनल.[82][106] One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain.[82] Supplemental magnesium[नोट 13] treatment has been shown to reduce amphetamine आत्म प्रशासन (i.e., doses given to oneself) in humans, but it is not an effective monotherapy for amphetamine addiction.[82]

A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in RCTs for amphetamine and methamphetamine addiction;[103] it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration.[103] There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion, मिर्टाज़पाइन, सेर्टालाइन), antipsychotics (aripiprazole), anticonvulsants (टोपिरामेट, Baclofen, gabapentin), naltrexone, varenicline, citicoline, ondansetron, prometa, riluzole, atomoxetine, dextroamphetamine, and modafinil.[103]

व्यवहार उपचार

A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that संयोजन चिकित्सा दोनोंके साथ contingency management तथा community reinforcement approach had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate).[107] Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, संज्ञानात्मक व्यवहारवादी रोगोपचार, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy, and other combination therapies involving these.[107]

Additionally, research on the neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., मैराथन दौड़ रहा है), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction.[sources 9] Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions.[87][89][108] विशेष रूप से, एरोबिक व्यायाम decreases psychostimulant self-administration, reduces the बहाली (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D2 (DRD2) density in the स्ट्रिएटम.[86][108] This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density.[86] One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or खाका: nowrap immunoreactivity in the striatum or other parts of the पुरस्कार प्रणाली.[88] Template:FOSB addiction table

Dependence and withdrawal

दवा की सहिष्णुता develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect.[109][110] According to a Cochrane review on वापसी in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose."[111] This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for खाका: nowrap weeks with a marked "crash" phase occurring during the first week.[111] Amphetamine withdrawal symptoms can include anxiety, drug craving, उदास मन, थकान, भूख बढ़ गई, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and सुहावने सपने.[111] The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence.[111] Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose.[32]

अधिमात्रा

An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care.[32][68][112] The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine.[21][68] Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose.[68] Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and खाने.[9][21] In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an "amphetamine use disorder" resulted in an estimated 3,788 deaths worldwide (खाका: nowrap लोगों की मृत्यु, 95% विश्वास).[नोट 14][113]

Overdose symptoms by system
प्रणाली Minor or moderate overdose[9][21][68] Severe overdose[sources 12]
कार्डियोवास्कुलर
Central nervous
प्रणाली
musculoskeletal
श्वसन
  • तेजी से साँस लेने
मूत्र
अन्य

विषैलापन

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized by dopamine अंतिम अध: पतन and reduced transporter and receptor function.[115][116] There is no evidence that amphetamine is directly neurotoxic in humans.[117][118] However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of hyperpyrexia, the excessive formation of प्रतिक्रियाशील प्राणवायु प्रजातियोंऔर बढ़ गया autoxidation of dopamine.[sources 13] Animal models of neurotoxicity from high-dose amphetamine exposure indicate that the occurrence of hyperpyrexia (i.e., core body temperature ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity.[116] Prolonged elevations of brain temperature above 40 °C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing मस्तिष्क की खून का अवरोध permeability.[116]

मनोविकृति

साँचा: देखिये An amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia.[22][23] A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about खाका: nowrap of users fail to recover completely.[22][121] According to the same review, there is at least one trial that shows मनोरोग प्रतिरोधी medications effectively resolve the symptoms of acute amphetamine psychosis.[22] Psychosis rarely arises from therapeutic use.[9][23][24]

दवा बातचीतटेम्पलेट: एंकर

साँचा: देखिये Many types of substances are known to बातचीत with amphetamine, resulting in altered drug action or चयापचय of amphetamine, the interacting substance, or both.[9] Inhibitors of enzymes that metabolize amphetamine (e.g., CYP2D6 तथा FMO3) will prolong its elimination half-life, meaning that its effects will last longer.[122][9] Amphetamine also interacts with टेम्पलेट: Abbr, खासकर monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase प्लाज्मा catecholamines (i.e., norepinephrine and dopamine);[9] therefore, concurrent use of both is dangerous.[9] Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of शामक तथा अवसाद and increase the effects of उत्तेजक तथा antidepressants.[9] Amphetamine may also decrease the effects of antihypertensives तथा मनोविकार नाशक due to its effects on blood pressure and dopamine respectively.[9] Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD.[नोट 15][127]

In general, there is no significant interaction when consuming amphetamine with food, but the pH of gastrointestinal content and urine affects the अवशोषण तथा मलत्याग of amphetamine, respectively.[9] Acidic substances reduce the absorption of amphetamine and increase urinary excretion, and alkaline substances do the opposite.[9] Due to the effect pH has on absorption, amphetamine also interacts with gastric acid reducers such as proton pump inhibitors तथा H2 एंटीथिस्टेमाइंस, which increase gastrointestinal pH (i.e., make it less acidic).[9]

औषध

pharmacodynamics

टेम्पलेट: के लिए Template:Amphetamine pharmacodynamics Amphetamine exerts its behavioral effects by altering the use of monoamines as neuronal signals in the brain, primarily in catecholamine neurons in the reward and executive function pathways of the brain.[19][42] The concentrations of the main neurotransmitters involved in reward circuitry and executive functioning, dopamine and norepinephrine, increase dramatically in a dose-dependent manner by amphetamine because of its effects on monoamine transporters.[19][42][128] प्रवेश मजबूत तथा प्रेरक नमस्कार-promoting effects of amphetamine are due mostly to enhanced dopaminergic activity in the मेसोलींबिक मार्ग.[7] प्रवेश जश्न and locomotor-stimulating effects of amphetamine are dependent upon the magnitude and speed by which it increases synaptic dopamine and norepinephrine concentrations in the स्ट्रिएटम.[5]

Amphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a खाका: nowrap तथा खाका: nowrap जी प्रोटीन-युग्मित रिसेप्टर (GPCR) discovered in 2001, which is important for regulation of brain monoamines.[19][129] का सक्रियण टेम्पलेट: Abbr बढ़ जाती है टेम्पलेट: Abbrlink production via adenylyl cyclase activation and inhibits monoamine transporter समारोह.[19][130] Monoamine autoreceptors (जैसे, D2 कम, presynaptic α2, तथा presynaptic 5-HT1A) have the opposite effect of TAAR1, and together these receptors provide a regulatory system for monoamines.[19][20] Notably, amphetamine and trace amines possess high binding affinities for TAAR1, but not for monoamine autoreceptors.[19][20] Imaging studies indicate that monoamine reuptake inhibition by amphetamine and trace amines is site specific and depends upon the presence of TAAR1 खाका: nowrap in the associated monoamine neurons.[19]

In addition to the neuronal monoamine transporters, amphetamine also inhibits both vesicular monoamine transporters, VMAT1 तथा VMAT2, के रूप में के रूप में अच्छी तरह से SLC1A1, SLC22A3, तथा SLC22A5.[sources 14] SLC1A1 is excitatory amino acid transporter 3 (EAAT3), a glutamate transporter located in neurons, SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine ट्रांसपोर्टर।[sources 14] Amphetamine is known to strongly induce cocaine- and amphetamine-regulated transcript (CART) जीन की अभिव्यक्ति,[137][138] a न्यूरोपेप्टाइड involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival इन विट्रो में.[137][139][140] The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique खाका: nowrap टेम्पलेट: Abbr.[140][141] Amphetamine also inhibits monoamine oxidases at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines.[1][142] In humans, the only post-synaptic receptor at which amphetamine is known to bind is the [[5-HT1A receptor|खाका: nowrap receptor]], where it acts as an agonist with low micromolar आत्मीयता।[143][144]

The full profile of amphetamine's short-term drug effects in humans is mostly derived through increased cellular communication or neurotransmission of डोपामाइन,[19] serotonin,[19] norepinephrine,[19] एपिनेफ्रीन,[128] हिस्टामिन,[128] CART peptides,[137][138] endogenous opioids,[145][146][147] एड्रेनोकॉर्टिकोट्रॉपिक हॉर्मोन,[148][149] corticosteroids के,[148][149] तथा ग्लूटामेट,[131][133] which it effects through interactions with टेम्पलेट: Abbr, खाका: nowrap, टेम्पलेट: Abbr, टेम्पलेट: Abbr, टेम्पलेट: Abbr, टेम्पलेट: Abbr, and possibly other biological targets.[sources 15] Amphetamine also activates seven human carbonic anhydrase enzymes, several of which are expressed in the human brain.[150]

Dextroamphetamine is a more potent agonist of टेम्पलेट: Abbr than levoamphetamine.[151] Consequently, dextroamphetamine produces greater टेम्पलेट: Abbr stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects.[21][151]

डोपामाइन

In certain brain regions, amphetamine increases the concentration of dopamine in the synaptic cleft.[19] Amphetamine can enter the presynaptic neuron either through टेम्पलेट: Abbr or by diffusing across the neuronal membrane directly.[19] As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter.[19] Upon entering the presynaptic neuron, amphetamine activates टेम्पलेट: Abbr which, through protein kinase A (PKA) and protein kinase C (PKC) signaling, causes DAT फास्फारिलीकरण.[19] Phosphorylation by either protein kinase can result in DAT internalization (खाका: nowrap reuptake inhibition), but खाका: nowrap phosphorylation alone induces the reversal of dopamine transport through DAT (i.e., dopamine efflux).[नोट 15][19][152] Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through an unidentified Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent pathway, in turn producing dopamine efflux.[129][131][153] Through direct activation of G protein-coupled inwardly-rectifying potassium channels, टेम्पलेट: Abbr reduces the firing rate of dopamine neurons, preventing a hyper-dopaminergic state.[154][155][156]

Amphetamine is also a substrate for the presynaptic vesicular monoamine transporter, टेम्पलेट: Abbr.[128][157] Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in the release of dopamine molecules from synaptic vesicles into the cytosol via dopamine efflux through VMAT2.[128][157] Subsequently, the cytosolic dopamine molecules are released from the presynaptic neuron into the synaptic cleft via reverse transport at टेम्पलेट: Abbr.[19][128][157]

norepinephrine

Similar to dopamine, amphetamine dose-dependently increases the level of synaptic norepinephrine, the direct precursor of एपिनेफ्रीन.[29][42] Based upon neuronal टेम्पलेट: Abbr टेम्पलेट: Abbr expression, amphetamine is thought to affect norepinephrine analogously to dopamine.[19][128][152] In other words, amphetamine induces TAAR1-mediated efflux and खाका: nowrap reuptake inhibition at phosphorylated टेम्पलेट: Abbr, competitive NET reuptake inhibition, and norepinephrine release from टेम्पलेट: Abbr.[19][128]

सेरोटोनिन

Amphetamine exerts analogous, yet less pronounced, effects on serotonin as on dopamine and norepinephrine.[19][42] Amphetamine affects serotonin via टेम्पलेट: Abbr and, like norepinephrine, is thought to phosphorylate टेम्पलेट: Abbr के माध्यम से टेम्पलेट: Abbr.[19][128] Like dopamine, amphetamine has low, micromolar affinity at the human 5-HT1A रिसेप्टर.[143][144]

Other neurotransmitters, peptides, hormones, and enzymes

मानव carbonic anhydrase
activation potency
किण्वक KA (टेम्पलेट: Abbrlink) सूत्रों का कहना है
hCA4 94 [150]
hCA5A 810 [150][158]
hCA5B 2560 [150]
hCA7 910 [150][158]
hCA12 640 [150]
hCA13 24100 [150]
hCA14 9150 [150]

Acute amphetamine administration in humans increases endogenous opioid release in several brain structures in the पुरस्कार प्रणाली.[145][146][147] Extracellular levels of ग्लूटामेट, the primary excitatory neurotransmitter in the brain, have been shown to increase in the striatum following exposure to amphetamine.[131] This increase in extracellular glutamate presumably occurs via the amphetamine-induced internalization of EAAT3, a glutamate reuptake transporter, in dopamine neurons.[131][133] Amphetamine also induces the selective release of हिस्टामिन से मस्तूल कोशिकाएं and efflux from histaminergic neurons पूज्य गुरुदेव के मार्गदर्शन से संपन्न कर सकते हैं - टेम्पलेट: Abbr.[128] Acute amphetamine administration can also increase एड्रेनोकॉर्टिकोट्रॉपिक हॉर्मोन तथा corticosteroid levels in रक्त प्लाज़्मा by stimulating the hypothalamic–pituitary–adrenal axis.[16][148][149]

In December 2017, the first study assessing the interaction between amphetamine and human carbonic anhydrase enzymes was published;[150] of the eleven carbonic anhydrase enzymes it examined, it found that amphetamine potently activates seven, four of which are highly expressed in the मानव मस्तिष्क, with low nanomolar through low micromolar activating effects.[150] Based upon preclinical research, cerebral carbonic anhydrase activation has cognition-enhancing effects;[159] but, based upon the clinical use of carbonic anhydrase inhibitors, carbonic anhydrase activation in other tissues may be associated with adverse effects, such as आंख का activation exacerbating आंख का रोग.[159]

फार्माकोकायनेटिक्स

The oral जैव उपलब्धता of amphetamine varies with gastrointestinal pH;[9] यह अच्छी तरह से है को अवशोषित from the gut, and bioavailability is typically over 75% for dextroamphetamine.[160] Amphetamine is a weak base with a pKa 9.9 का;[161] consequently, when the pH is basic, more of the drug is in its लिपिड घुलनशील free base form, and more is absorbed through the lipid-rich कोशिका की झिल्लियाँ of the gut epithelium.[161][9] Conversely, an acidic pH means the drug is predominantly in a water-soluble धनायनित (salt) form, and less is absorbed.[161] लगभग खाका: nowrap of amphetamine circulating in the bloodstream is bound to plasma proteins.[137] Following absorption, amphetamine readily वितरित into most tissues in the body, with high concentrations occurring in मस्तिष्कमेरु द्रव तथा मस्तिष्क ऊतक।[162]

प्रवेश half-lives of amphetamine enantiomers differ and vary with urine pH.[161] At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are खाका: nowrap hours and खाका: nowrap hours, respectively.[161] Highly acidic urine will reduce the enantiomer half-lives to 7 hours;[162] highly alkaline urine will increase the half-lives up to 34 hours.[162] The immediate-release and extended release variants of salts of both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively.[161] Amphetamine is सफाया के माध्यम से गुर्दे, साथ में खाका: nowrap of the drug being excreted unchanged at normal urinary pH.[161] When the urinary pH is basic, amphetamine is in its free base form, so less is excreted.[161] When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively.[161] Following oral administration, amphetamine appears in urine within 3 hours.[162] Roughly 90% of ingested amphetamine is eliminated 3 days after the last oral dose.[162]Template:If pagename

CYP2D6, dopamine β-hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butyrate-CoA ligase (XM-ligase), and ग्लाइसिन N-acyltransferase (GLYAT) are the enzymes known to metabolize amphetamine or its metabolites in humans.[sources 16] Amphetamine has a variety of excreted metabolic products, including खाका: nowrap, खाका: nowrap, खाका: nowrap, बेंज़ोइक अम्ल, hippuric acid, norephedrine, तथा phenylacetone.[161][163] Among these metabolites, the active sympathomimetics रहे खाका: nowrap,[164] खाका: nowrap,[165] and norephedrine.[166] The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.[161][167] The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following: Template:Amphetamine pharmacokinetics खाका: साफ

Pharmacomicrobiomics

प्रवेश human metagenome (i.e., the genetic composition of an individual and all microorganisms that reside on or within the individual's body) varies considerably between individuals.[168][169] Since the total number of microbial and viral cells in the human body (over 100 trillion) greatly outnumbers human cells (tens of trillions),[नोट 16][168][170] there is considerable potential for interactions between drugs and an individual's microbiome, including: drugs altering the composition of the मानव माइक्रोबियम, दवा चयापचय by microbial enzymes modifying the drug's pharmacokinetic profile, and microbial drug metabolism affecting a drug's clinical efficacy and विषाक्तता प्रोफ़ाइल।[168][169][171] The field that studies these interactions is known as pharmacomicrobiomics.[168]

Similar to most जैविक अणुओं अन्य और orally administered xenobiotics (i.e., drugs), amphetamine is predicted to undergo promiscuous metabolism by human gastrointestinal microbiota (primarily bacteria) prior to absorption into the रक्त प्रवाह.[171] The first amphetamine-metabolizing microbial enzyme, tyramine oxidase from a strain of ई. कोलाई commonly found in the human gut, was identified in 2019.[171] This enzyme was found to metabolize amphetamine, tyramine, and phenethylamine with roughly the same binding affinity for all three compounds.[171]

Related endogenous compounds

टेम्पलेट: विवरण Amphetamine has a very similar structure and function to the अंतर्जात trace amines, which are naturally occurring neuromodulator molecules produced in the human body and brain.[19][29][172] Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and खाका: nowrap, एक समाजिक of amphetamine (i.e., it has an identical molecular formula).[19][29][173] In humans, phenethylamine is produced directly from खाका: nowrap द्वारा aromatic amino acid decarboxylase (AADC) enzyme, which converts खाका: nowrap into dopamine as well.[29][173] के बदले में, खाका: nowrap is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine.[29][173] Like amphetamine, both phenethylamine and खाका: nowrap regulate monoamine neurotransmission via टेम्पलेट: Abbr;[19][172][173] unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.[29][173]

रसायन विज्ञान

Template:Annotated image 4 साँचा: एकाधिक छवि Amphetamine is a मिथाइल मुताबिक़ of the mammalian neurotransmitter phenethylamine with the chemical formula Template:Chemical formula. The carbon atom adjacent to the primary amine एक stereogenic center, and amphetamine is composed of a racemic 1:1 mixture of two एनंटीओमर.[2] This racemic mixture can be separated into its optical isomers:[नोट 17] levoamphetamine तथा dextroamphetamine.[2] At room temperature, the pure free base of amphetamine is a mobile, colorless, and परिवर्तनशील तरल with a characteristically strong अमाइन odor, and acrid, burning taste.[174] Frequently prepared solid salts of amphetamine include amphetamine adipate,[175] aspartate,[9] hydrochloride,[176] फॉस्फेट,[177] saccharate,[9] sulfate,[9] and tannate.[178] Dextroamphetamine sulfate is the most common enantiopure salt.[30] Amphetamine is also the parent compound of its own structural class, which includes a number of psychoactive डेरिवेटिव.[28][2] In organic chemistry, amphetamine is an excellent chiral ligand के लिए stereoselective synthesis of खाका: nowrap.[179]

Substituted derivatives

साँचा: मुख्य सूची The substituted derivatives of amphetamine, or "substituted amphetamines", are a broad range of chemicals that contain amphetamine as a "backbone";[28][31][180] specifically, this chemical class शामिल यौगिक compounds that are formed by replacing one or more hydrogen atoms in the amphetamine core structure with substituents.[28][31][181] The class includes amphetamine itself, stimulants like methamphetamine, serotonergic empathogens पसंद एमडीएमए, तथा decongestants पसंद इफेड्रिन, among other subgroups.[28][31][180]

संश्लेषण

टेम्पलेट: विवरण Since the first preparation was reported in 1887,[182] numerous synthetic routes to amphetamine have been developed.[183][184] The most common route of both legal and illicit amphetamine synthesis employs a non-metal reduction known as the लीकर्ट प्रतिक्रिया (method 1).[30][185] In the first step, a reaction between phenylacetone and formamide, either using additional फॉर्मिक एसिड or formamide itself as a reducing agent, yields खाका: nowrap. This intermediate is then hydrolyzed using hydrochloric acid, and subsequently basified, extracted with organic solvent, concentrated, and distilled to yield the free base. The free base is then dissolved in an organic solvent, sulfuric acid added, and amphetamine precipitates out as the sulfate salt.[185][186]

का एक नंबर chiral resolutions have been developed to separate the two enantiomers of amphetamine.[183] For example, racemic amphetamine can be treated with खाका: nowrap एक के लिए फार्म diastereoisomeric salt which is fractionally crystallized to yield dextroamphetamine.[187] Chiral resolution remains the most economical method for obtaining optically pure amphetamine on a large scale.[188] In addition, several enantioselective syntheses of amphetamine have been developed. In one example, optically pure खाका: nowrap is condensed with phenylacetone to yield a chiral शिफ बेस. In the key step, this intermediate is reduced by catalytic hydrogenation with a transfer of chirality to the carbon atom alpha to the amino group. Cleavage of the benzylic amine bond by hydrogenation yields optically pure dextroamphetamine.[188]

A large number of alternative synthetic routes to amphetamine have been developed based on classic organic reactions.[183][184] एक उदाहरण है Friedel–Crafts alkylation of बेंजीन by एलिल क्लोराइड to yield beta chloropropylbenzene which is then reacted with ammonia to produce racemic amphetamine (method 2).[189] Another example employs the Ritter reaction (method 3). In this route, allylbenzene is reacted acetonitrile in sulfuric acid to yield an organosulfate which in turn is treated with sodium hydroxide to give amphetamine via an acetamide intermediate.[190][191] A third route starts with खाका: nowrap which through a double alkylation with methyl iodide द्वारा पीछा benzyl chloride can be converted into खाका: nowrap acid. This synthetic intermediate can be transformed into amphetamine using either a Hofmann or Curtius rearrangement (method 4).[192]

A significant number of amphetamine syntheses feature a कमी एक की निट्रो, imine, oxime, or other nitrogen-containing कार्यात्मक समूह.[184] In one such example, a Knoevenagel condensation of benzaldehyde साथ में nitroethane पैदावार खाका: nowrap. The double bond and nitro group of this intermediate is कम हो using either catalytic हाइड्रोजनीकरण or by treatment with लिथियम एल्यूमीनियम हाइड्राइड (method 5).[185][193] Another method is the reaction of phenylacetone साथ में अमोनिया, producing an imine intermediate that is reduced to the primary amine using hydrogen over a palladium catalyst or lithium aluminum hydride (method 6).[185]

Amphetamine synthetic routes
साँचा: एकाधिक छवि
साँचा: एकाधिक छवि

खाका: साफ

Detection in body fluids

Amphetamine is frequently measured in urine or blood as part of a ड्रग परीक्षण for sports, employment, poisoning diagnostics, and forensics.[sources 17] जैसे तकनीक immunoassay, which is the most common form of amphetamine test, may cross-react with a number of sympathomimetic drugs.[197] Chromatographic methods specific for amphetamine are employed to prevent false positive results.[198] Chiral separation techniques may be employed to help distinguish the source of the drug, whether prescription amphetamine, prescription amphetamine prodrugs, (e.g., selegiline), बिना डॉक्टर की सलाह पर बेची जाने वाली दवाएं products that contain levomethamphetamine,[नोट 18] or illicitly obtained substituted amphetamines.[198][201][202] Several prescription drugs produce amphetamine as a मेटाबोलाइटसहित, benzphetamine, clobenzorex, famprofazone, fenproporex, lisdexamfetamine, mesocarb, methamphetamine, prenylamine, तथा selegiline, दूसरों के बीच.[5][203][204] These compounds may produce positive results for amphetamine on drug tests.[203][204] Amphetamine is generally only detectable by a standard drug test for approximately 24 hours, although a high dose may be detectable for खाका: nowrap दिन.[197]

For the assays, a study noted that an enzyme multiplied immunoassay technique (EMIT) assay for amphetamine and methamphetamine may produce more false positives than liquid chromatography–tandem mass spectrometry.[201] Gas chromatography–mass spectrometry (GC–MS) of amphetamine and methamphetamine with the derivatizing agent खाका: nowrap chloride allows for the detection of methamphetamine in urine.[198] GC–MS of amphetamine and methamphetamine with the chiral derivatizing agent Mosher's acid chloride allows for the detection of both dextroamphetamine and dextromethamphetamine in urine.[198] Hence, the latter method may be used on samples that test positive using other methods to help distinguish between the various sources of the drug.[198]

History, society, and culture

टेम्पलेट: मुख्य Template:Global estimates of illegal drug users Amphetamine was first synthesized in 1887 in Germany by Romanian chemist Lazăr Edeleanu who named it phenylisopropylamine;[182][205][206] its stimulant effects remained unknown until 1927, when it was independently resynthesized by Gordon Alles and reported to have sympathomimetic गुण।[206] Amphetamine had no medical use until late 1933, when Smith, Kline and French began selling it as an साँस लेनेवाला under the brand name Benzedrine as a decongestant.[10] Benzedrine sulfate was introduced 3 years later and was used to treat a wide variety of चिकित्सा की स्थितिसहित, narcolepsy, मोटापा, निम्न रक्तचाप, कम कामेच्छा, तथा पुराने दर्द, दूसरों के बीच.[33][10] During World War II, amphetamine and methamphetamine were used extensively by both the Allied and Axis forces for their stimulant and performance-enhancing effects.[182][207][208] As the addictive properties of the drug became known, governments began to place strict controls on the sale of amphetamine.[182] For example, during the early 1970s in the United States, amphetamine became a schedule II controlled substance नीचे नियंत्रित पदार्थ अधिनियम.[209][210] In spite of strict government controls, amphetamine has been used legally or illicitly by people from a variety of backgrounds, including authors,[211] musicians,[212] mathematicians,[213] और एथलीटों।[8]

Amphetamine is still illegally synthesized today in गुप्त लैब्स and sold on the काला बाजार, primarily in European countries.[214] Among European Union (EU) member states साँचा: के रूप में 11.9 million adults of ages खाका: nowrap have used amphetamine or methamphetamine at least once in their lives and 1.7 million have used either in the last year.[215] During 2012, approximately 5.9 मीट्रिक टन of illicit amphetamine were seized within EU member states;[216] the "street price" of illicit amphetamine within the EU ranged from खाका: nowrap per gram during the same period.[216] Outside Europe, the illicit market for amphetamine is much smaller than the market for methamphetamine and MDMA.[214]

कानूनी हैसियत

के परिणामस्वरूप संयुक्त राष्ट्र 1971 Convention on Psychotropic Substances, amphetamine became a schedule II controlled substance, as defined in the treaty, in all 183 state parties.[11] Consequently, it is heavily regulated in most countries.[217][218] Some countries, such as South Korea and Japan, have banned substituted amphetamines even for medical use.[219][220] In other nations, such as Canada (schedule I drug),[221] the Netherlands (List I drug),[222] the United States (schedule II drug),[9] ऑस्ट्रेलिया (अनुसूची 8),[223] Thailand (category 1 narcotic),[224] and United Kingdom (class B drug),[225] amphetamine is in a restrictive national drug schedule that allows for its use as a medical treatment.[214][12]

दवा उत्पाद

Several currently marketed amphetamine formulations contain both enantiomers, including those marketed under the brand names Adderall, Adderall XR, Mydayis,[नोट 19] Adzenys ER, खाका: nowrap, Dyanavel XR, Evekeo, and Evekeo ODT. Of those, Evekeo (including Evekeo ODT) is the only product containing only racemic amphetamine (as amphetamine sulfate), and is therefore the only one whose active moiety can be accurately referred to simply as “amphetamine.”[32][16][72] Dextroamphetamine, marketed under the brand names Dexedrine and Zenzedi, is the only enantiopure amphetamine product currently available. A प्रोड्रग form of dextroamphetamine, lisdexamfetamine, is also available and is marketed under the brand name Vyvanse. As it is a prodrug, lisdexamfetamine is structurally different from dextroamphetamine, and is inactive until it metabolizes into dextroamphetamine.[17][226] The free base of racemic amphetamine was previously available as Benzedrine, Psychedrine, and Sympatedrine.[5] Levoamphetamine was previously available as Cydril.[5] Many current amphetamine pharmaceuticals are लवण due to the comparatively high volatility of the free base.[5][17][30] However, oral suspension and orally disintegrating tablet (ODT) dosage forms composed of the free base were introduced in 2015 and 2016, respectively.[72][227][228] Some of the current brands and their generic equivalents are listed below.

Amphetamine pharmaceuticals
ब्रांड
नाम
संयुक्त राज्य अमेरिका
Adopted Name
(D:L) ratio
खुराक
प्रपत्र
विपणन
दिनांक प्रारंभ
US consumer
price data
सूत्रों का कहना है
Adderall - 3: 1 (salts) गोली 1996 GoodRx [5][17]
Adderall XR - 3: 1 (salts) कैप्सूल 2001 GoodRx [5][17]
Mydayis - 3: 1 (salts) कैप्सूल 2017 GoodRx [229][230]
Adzenys ER एम्फ़ैटेमिन 3: 1 (आधार) निलंबन 2017 GoodRx [231]
खाका: nowrap एम्फ़ैटेमिन 3: 1 (आधार) Odt 2016 GoodRx [228][232]
Dyanavel XR एम्फ़ैटेमिन 3.2: 1 (आधार) निलंबन 2015 GoodRx [72][227]
Evekeo amphetamine sulfate 1: 1 (salts) गोली 2012 GoodRx [16][233]
Evekeo ODT amphetamine sulfate 1: 1 (salts) Odt 2019 GoodRx [234]
Dexedrine dextroamphetamine sulfate 1: 0 (salts) कैप्सूल 1976 GoodRx [5][17]
Zenzedi dextroamphetamine sulfate 1: 0 (salts) गोली 2013 GoodRx [17][235]
Vyvanse lisdexamfetamine dimesylate 1: 0 (prodrug) कैप्सूल 2007 GoodRx [5][226][236]
गोली

Template:Amphetamine base in marketed amphetamine medications

नोट्स

टेम्पलेट: Reflist

Image legend

टेम्पलेट: Reflist

Reference notes

टेम्पलेट: Reflist

संदर्भ

टेम्पलेट: Reflist

बाहरी लिंक

Template:Amphetamine Template:ADHD pharmacotherapies Template:TAAR ligands Template:Monoamine releasing agents Template:Phenethylamines Template:Drug use साँचा: पोर्टल बार

साँचा: चुनिंदा लेख

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    Figure 3: Treatment benefit by treatment type and outcome group
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  209. साँचा: वेब का हवाला देते हैं
  210. साँचा: वेब का हवाला देते हैं
  211. साँचा: वेब का हवाला देते हैं
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  213. साँचा: वेब का हवाला देते हैं
  214. 214.0 214.1 214.2 साँचा: वेब का हवाला देते हैं
  215. साँचा: वेब का हवाला देते हैं
  216. 216.0 216.1 साँचा: उद्धृत रिपोर्ट
  217. साँचा: पुस्तक का हवाला देते हैं
  218. साँचा: वेब का हवाला देते हैं
  219. साँचा: वेब का हवाला देते हैं
  220. साँचा: वेब का हवाला देते हैं
  221. साँचा: वेब का हवाला देते हैं
  222. साँचा: वेब का हवाला देते हैं
  223. साँचा: विश्वकोश का हवाला देते हैं
  224. साँचा: वेब का हवाला देते हैं
  225. साँचा: वेब का हवाला देते हैं
  226. 226.0 226.1 उद्धृत त्रुटि: अमान्य है <ref> टैग; नाम के लिए कोई पाठ उपलब्ध नहीं कराया गया था USVyvanselabel
  227. 227.0 227.1 साँचा: वेब का हवाला देते हैं
  228. 228.0 228.1 साँचा: वेब का हवाला देते हैं
  229. साँचा: वेब का हवाला देते हैं
  230. साँचा: वेब का हवाला देते हैं
  231. साँचा: वेब का हवाला देते हैं
  232. साँचा: वेब का हवाला देते हैं
  233. साँचा: वेब का हवाला देते हैं
  234. साँचा: वेब का हवाला देते हैं
  235. साँचा: वेब का हवाला देते हैं
  236. साँचा: वेब का हवाला देते हैं


उद्धृत त्रुटि: <ref> टैग "नोट" नामक समूह के लिए मौजूद हैं, लेकिन इसके अनुरूप नहीं है <references group="note"/> टैग मिला, या एक समापन </ Ref> लापता है
उद्धृत त्रुटि: <ref> tags exist for a group named "sources", but no corresponding <references group="sources"/> टैग मिला, या एक समापन </ Ref> लापता है