Description

Simple

A medication used to treat ADHD.

Clinical

A CNS stimulant and sympathomimetic agent indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).

Overview

Amphetamine, a compound discovered over 100 years ago, is one of the more restricted controlled drugs. It was previously used for a large variety of conditions and this changed until this point where its use is highly restricted. Amphetamine, with the chemical formula alpha-methylphenethylamine, was discovered in 1910 and first synthesized by 1927. After being proven to reduce drug-induced anesthesia and produce arousal and insomnia, amphetamine racemic mix was registered by Smith, Kline and French in 1935. Amphetamine structure presents one chiral center and it exists in the form of dextro- and levo-isomers.[1] The first product of Smith, Kline and French was approved by the FDA on 1976.[12]

During World War II, amphetamine was used to promote wakefulness in the soldiers. This use derived into a large overproduction of amphetamine and all the surplus after the war finalized ended up in the black market, producing the initiation of the illicit abuse.[Read more

Pharmacology

Indication

Amphetamine is indicated for the treatment of attention-deficit/hyperactivity disorders (ADHD) as well as for the treatment of central nervous system disorders such as narcolepsy.[ Read more

Pharmacodynamic

From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce card... Read more

Mechanism of action

It is important to consider that amphetamine has a very similar structure to the catecholamine neurotransmitters mainly on the presence of a long planar conformation, the presence of an aromatic ring and nitrogen in the aryl side chain. Amphetamine, as well as other catecholamines, is taken into pre... Read more

Absorption

Amphetamine is well absorbed in the gut and as it is a weak base hence the more basic the environment the more of the drug is found in a lipid-soluble form and the absorption through lipid-rich cell membranes is highly favored.[ Read more

Protein binding

The reported protein binding of amphetamine is relatively low and register to be of 20%.[ Read more

Volume of distribution

Amphetamine is reported to have a high volume of distribution of 4 L/kg.[ Read more

Clearance

The reported normal clearance rate is of 0.7 L.h/kg. This clearance has been shown to get significantly reduced in patients with renal impairment reaching a value of 0.4 L.h/kg.[17]

Half life

The half-life of amphetamine highly depends on the isomer. For d-amphetamine, the reported half-life is of approximately 9-11 hours while for l-amphetamine the half-life is reported to be of 11-14 hours. The urine pH can modify this pharmacokinetic parameter which can vary from 7 hours in acid urine... Read more

Route of elimination

The elimination of amphetamine is mainly via the urine from which about 40% of the excreted dose is found as unchanged amphetamine. About 90% of the administered amphetamine is eliminated 3 days after oral administration.[ Read more

Toxicity

The mean lethal serum concentration is reported to be of 6.4 mg/l. Acute amphetamine overdose can lead to hyperthermia, respiratory depression, seizures, metabolic acidosis, renal failure, hepatic injury, and coma. Some of the neurologic effects have been shown to be agitation, aggressive behavior,... Read more

Adverse Effects

Contraindications

  • Hypersensitivity:
    • true
  • Regions: Canada
  • Regions: US
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: US
  • Patient Conditions:
      • Name: Advanced arteriosclerosis
      • Drugbank Id: DBCOND0107486
  • Regions: US
  • Patient Conditions:
      • Name: History of drug abuse
      • Drugbank Id: DBCOND0107489
  • Regions: US
  • Patient Conditions:
      • Name: Moderate to Severe Hypertension
      • Drugbank Id: DBCOND0042937
  • Regions: US
  • Patient Conditions:
      • Name: Symptomatic cardiovascular disease
      • Drugbank Id: DBCOND0107487
      • Modification Of:
        • Base:
          • Name: Cardiovascular Disease
          • Drugbank Id: DBCOND0028376
        • Severity:
          • Includes:
            • symptomatic
  • Regions: US
  • Patient Conditions:
      • Name: Agitated state
      • Drugbank Id: DBCOND0107488
  • Regions: US
  • Patient Conditions:
      • Name: Hyperthyroidism
      • Drugbank Id: DBCOND0009048

Food Interactions

  • Take with or without food.

Interactions

Type in a drug name to check for interaction with Amphetamine
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The risk or severity of bleeding and hemorrhage can be increased when Amphetamine is combined with (R)-warfarin.
(S)-Warfarin
The risk or severity of bleeding and hemorrhage can be increased when Amphetamine is combined with (S)-Warfarin.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Amphetamine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
1-benzylimidazole
The therapeutic efficacy of 1-benzylimidazole can be decreased when used in combination with Amphetamine.
2,4-thiazolidinedione
Amphetamine may increase the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
Amphetamine may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
Amphetamine may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthine
The risk or severity of adverse effects can be increased when Amphetamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,5-diiodothyropropionic acid
The risk or severity of adverse effects can be increased when Amphetamine is combined with 3,5-diiodothyropropionic acid.
3,5-Diiodotyrosine
The risk or severity of adverse effects can be increased when Amphetamine is combined with 3,5-Diiodotyrosine.
4-Bromo-2,5-dimethoxyamphetamine
Amphetamine may increase the hypertensive activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin
The risk or severity of bleeding and hemorrhage can be increased when Amphetamine is combined with 4-hydroxycoumarin.
4-Methoxyamphetamine
Amphetamine may increase the hypertensive activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Amphetamine.
6-O-benzylguanine
The risk or severity of adverse effects can be increased when Amphetamine is combined with 6-O-benzylguanine.
7-Deazaguanine
The risk or severity of adverse effects can be increased when Amphetamine is combined with 7-Deazaguanine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Amphetamine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypertensive activities of Amphetamine.
7,9-Dimethylguanine
The risk or severity of adverse effects can be increased when Amphetamine is combined with 7,9-Dimethylguanine.
8-azaguanine
The risk or severity of adverse effects can be increased when Amphetamine is combined with 8-azaguanine.
17 References
  1. 1 . Heal DJ, Smith SL, Gosden J, Nutt DJ: Amphetamine, past and present--a pharmacological and clinical perspective. J Psychopharmacol. 2013 Jun;27(6):479-96. doi: 10.1177/0269881113482532. Epub 2013 Mar 28.PubMed: 23539642
  2. 2 . Guttmann E, Sargant W: Observations on Benzedrine. Br Med J. 1937 May 15;1(3984):1013-5.PubMed: 20780662
  3. 3 . Arnold LE, Wender PH, McCloskey K, Snyder SH: Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms. Arch Gen Psychiatry. 1972 Dec;27(6):816-22.PubMed: 4564954
  4. 4 . Robertson SD, Matthies HJ, Galli A: A closer look at amphetamine-induced reverse transport and trafficking of the dopamine and norepinephrine transporters. Mol Neurobiol. 2009 Apr;39(2):73-80. doi: 10.1007/s12035-009-8053-4. Epub 2009 Feb 6.PubMed: 19199083
  5. 5 . Easton N, Steward C, Marshall F, Fone K, Marsden C: Effects of amphetamine isomers, methylphenidate and atomoxetine on synaptosomal and synaptic vesicle accumulation and release of dopamine and noradrenaline in vitro in the rat brain. Neuropharmacology. 2007 Feb;52(2):405-14. doi: 10.1016/j.neuropharm.2006.07.035. Epub 2006 Oct 3.PubMed: 17020775
  6. 6 . Baumann MH, Ayestas MA, Dersch CM, Brockington A, Rice KC, Rothman RB: Effects of phentermine and fenfluramine on extracellular dopamine and serotonin in rat nucleus accumbens: therapeutic implications. Synapse. 2000 May;36(2):102-13. doi: 10.1002/(SICI)1098-2396(200005)36:2<102::AID-SYN3>3.0.CO;2-#.PubMed: 10767057
  7. 7 . BETT WR: Benzedrine sulphate in clinical medicine; a survey of the literature. Postgrad Med J. 1946 Aug;22:205-18.PubMed: 20997404
  8. 8 . Tarver J, Daley D, Sayal K: Attention-deficit hyperactivity disorder (ADHD): an updated review of the essential facts. Child Care Health Dev. 2014 Nov;40(6):762-74. doi: 10.1111/cch.12139. Epub 2014 Apr 14.PubMed: 24725022
  9. 9 . Kornum BR, Knudsen S, Ollila HM, Pizza F, Jennum PJ, Dauvilliers Y, Overeem S: Narcolepsy. Nat Rev Dis Primers. 2017 Feb 9;3:16100. doi: 10.1038/nrdp.2016.100.PubMed: 28179647
  10. 10 . Ricca V, Castellini G, Mannucci E, Monami M, Ravaldi C, Gorini Amedei S, Lo Sauro C, Rotella CM, Faravelli C: Amphetamine derivatives and obesity. Appetite. 2009 Apr;52(2):405-9. doi: 10.1016/j.appet.2008.11.013. Epub 2008 Dec 3.PubMed: 19103239
  11. 11 . de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S: Clinical pharmacokinetics of amfetamine and related substances: monitoring in conventional and non-conventional matrices. Clin Pharmacokinet. 2004;43(3):157-85. doi: 10.2165/00003088-200443030-00002.PubMed: 14871155
  12. 12 . FDA approvals Link
  13. 13 . JAMA network Link
  14. 14 . Australian Health Department Link
  15. 15 . Inchem Link
  16. 16 . D-amphetamine sulfate information Link
  17. 17 . EZETROL (amphetamine) Canadian label File