Dextroamphetamine

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Dextroamphetamine
Systematic (IUPAC) name
(2S)-1-phenylpropan-2-amine
Identifiers
CAS number	300-62-9
ATC code	N06BA01
PubChem	5826
DrugBank	APRD00480
Chemical data
Formula	C9H13N
Mol. mass	135.206 g/mol
Pharmacokinetic data
Bioavailability	>75%
Metabolism	Hepatic
Half life	10–28 hours (Average ~12 hours)
Excretion	Renal: ~45%
Therapeutic considerations
Pregnancy cat.	B3(AU) C(US)
Legal status	Controlled (S8)(AU) Schedule III(CA) Class B(UK) Schedule II(US)
Routes	Clinical: Oral, Intravenous, Sublingual Other: Vaporized, Insufflated, Suppository

Dextroamphetamine is a powerful psychostimulant which produces increased wakefulness, energy and self-confidence in association with decreased fatigue and appetite. It works primarily by inducing the release of the neurotransmitters dopamine and norepinephrine from their storage areas in nerve terminals. Other common names for dextroamphetamine include d-amphetamine, dexamphetamine, (S)-(+)-amphetamine, and brand names such as Dexedrine and Dextrostat.

Contents 1 Overview 2 History 3 Clinical uses 3.1 ADHD 3.2 Narcolepsy 3.3 Extreme Obesity 3.4 Depression 3.5 Experimental treatments 4 Other uses 5 Side effects 5.1 Overdose 6 Time course and elimination 7 See also 8 Images 9 References 10 Footnotes

[edit] Overview

Dextroamphetamine, commonly abbreviated as d-amphetamine, is the dextrorotary stereoisomer of the amphetamine molecule, which can take two different forms. Its stimulant properties are similar to those of methylphenidate and methamphetamine, though with a slower onset of action and a duration that lies somewhere between the two. It is perhaps the archetypal euphoric stimulant, and drugs with similar psychoactive properties are often referred to as "amphetamine analogues", or described as having "amphetamine-like", or even "amphetaminergic" effects.

Both dopamine and norepinephrine are significant in dextroamphetamine's mechanism of action. In broad terms, dopamine is responsible for boosting mental focus and mood, while norepinephrine causes the typical fight-or-flight effects of appetite-suppression, reduced sense of fatigue, dry mouth and increased blood pressure.^[1]

Dextroamphetamine is most often prescribed as dextroamphetamine sulfate, available as 5 mg and 10 mg tablets, as well as 5 mg, 10 mg, and 15 mg time-release capsules.

An example of a pharmaceutical that contains active ingredients in addition to dextroamphetamine is Adderall and Adderall generic derivatives. Their formulations contain sulfate and aspartate monohydrate salts of racemic d,l-amphetamine and also sulfate and saccharate salts of d-amphetamine. Aspartate, saccharate and sulfate salts differ pharmacokinetically in the rate at which they are metabolized by the body. Due to that reason, as well as others, Adderall's effects are different from pharmaceuticals with dextroamphetamine as an exculsive active ingredient.

[edit] History

Amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazar Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline, and French (currently known as GlaxoSmithKline) introduced it in the form of the "Benzedrine Inhaler," for combating cold symptoms. Notably, the chemical form of Benzedrine in the inhaler was the purely basic form (i.e., it was not a chloride or sulfate salt). In free-base form, amphetamine is a volatile oil, hence the efficacy of the inhalers.

Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically dextroamphetamine, and in 1937 Smith, Kline, and French introduced Dexedrine tablets, which consisted of pure dextroamphetamine sulfate (a salt of the basic form of D-amphetamine), under the tradename Dexedrine. In the United States, Dexedrine tablets were approved to treat narcolepsy, attention disorders, depression, and obesity. Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbiturate) sold under the tradename Dexamyl and, in the 1950s, an extended release capsule (the "Spansule").

It quickly became apparent that Dexedrine and other amphetamines had a high potential for abuse, although they were not heavily controlled until 1970, when the Comprehensive Drug Abuse Prevention and Control Act was passed by the United States Congress. Dexedrine, along with other sympathomimetics, was eventually classified as schedule II, the most restrictive category possible for a drug with recognized medical uses.

[edit] Clinical uses

[edit] ADHD

Dextroamphetamine is frequently used for treatment of attention deficit hyperactivity disorder (ADHD) In some localities it has replaced methylphenidate as the first-choice medication for ADHD, a role in which it is considered highly effective.

[edit] Narcolepsy

Dextroamphetamine is also used for well-established narcolepsy, generally where non-pharmacological measures have proved insufficient.

[edit] Extreme Obesity

It is occasionally prescribed for weight-loss in cases of extreme obesity.

[edit] Depression

The theraputic use of stimulants are occasionally prescribed alongside antidepressants for cases of extreme clinical depression. See above.

[edit] Experimental treatments

Though such use remains out of the mainstream, dextroamphetamine has been successfully applied in the treatment of certain categories of depression as well as other psychiatric syndromes.^[2] Such alternate uses include reduction of fatigue in cancer patients, antidepressant treatment for HIV patients with depression and debilitating fatigue,^[3] early stage physiotherapy for severe stroke victims,^[4]

[edit] Other uses

The U.S. Air Force uses dextroamphetamine as its "go-pill," given to pilots on long missions to help them remain focused and alert. Other branches of the U.S. military (as well as the armed forces of other nations) commonly use or have dispensed dextroamphetamine to troops to prevent or treat fatigue in combat situations. Because of the propensity of dextroamphetamine to cause behavioral side effects, this use is viewed as controversial;(Friendly Fire incidents are linked sometimes to the use if this drug and its effects on long term fatigued pilots)а newer stimulant medications with fewer side effects, like modafinil are being investigated for this reason. NASA has also used dextroamphetamine to combat fatigue in astronauts near the end of a mission.

Along with Ritalin, illicit use of dextroamphetamine has been reported among students, both as a study aid, and for purely recreational purposes. According to the National Institute on Drug Abuse, 4% of American college students reported non-prescription stimulant use in 2004.^[5]

[edit] Side effects

Documented side effects of the theraputic use of dextroamphetamine include sleeplessness, reduced appetite, and dryness of mouth.

[edit] Overdose

The Physician's 1991 Drug Handbook reports: "Symptoms of overdose include restlessness, tremor, hyperreflexia, tachypnea, confusion, aggressiveness, hallucinations, and panic." Dilated pupils are common with high doses.

The fatal dose in humans is not precisely known, but in various species of rat generally ranges between 50 and 100 mg/kg, or a factor of 100 over what is required to produce noticeable psychological effects.^[6][7] This suggests a wide therapeutic range, in contrast to such drugs as morphine and heroin, where effective doses may be as much as 50% of a fatal dose. Although the symptoms seen in a fatal overdose are similar to those of methamphetamine, their mechanisms are not identical, as some substances which inhibit d-amphetamine toxicity do not do so for methamphetamine.^[8][9]

An extreme symptom of overdose is amphetamine psychosis, characterized by vivid visual, auditory, and sometimes tactile hallucinations. Many of its symptoms are identical to the psychosis-like state which follows long-term sleep deprivation, so it remains unclear whether these are solely the effect of the drug, or due to the long periods of sleep deprivation which are often undergone by the chronic user or abuser. "In apparently sensitive individuals, psychosis may be produced by 55 to 75 mg of dextroamphetamine. With high enough doses, psychosis can probably be induced in anyone."^[10]

[edit] Time course and elimination

On average, about one half of a given dose is eliminated unchanged in the urine, while the other half is broken down into various metabolites (mostly benzoic acid).^[11] However, the drug's half-life is highly variable because the rate of excretion is very sensitive to urinary pH. Under alkaline conditions, direct excretion is negligible and 95%+ of the dose is metabolized. The main metabolic pathway is d-amphetamine phenylacetone benzoic acid hippuric acid. Another pathway, mediated by enzyme CYP2D6, is d-amphetamine p-hydroxyamphetamine p-hydroxynorephedrine. Although p-hydroxyamphetamine is a minor metabolite (~5% of the dose), it may may have significant physiological effects as a norepinephrine analogue.^[12]

Subjective effects are increased by larger doses, however, over the course of a given dose there is a noticeable divergence between such effects and drug concentration in the blood.^[13] In particular, mental effects peak before maximal blood levels are reached, and decline as blood levels remain stable or even continue to increase.^[14][15][16] This indicates a mechanism for development of acute tolerance, perhaps distinct from that seen in chronic use. Its slower onset of action as compared to methamphetamine and methylphenidate is presumably due to a somewhat lower effectiveness in crossing the blood-brain barrier.^[17]

[edit] See also

• ADHD
• Lisdexamfetamine
• Amphetamine formulations including dextroamphetamine:
  • Adderall
  • Benzedrine
• Related drugs:
  • Methylphenidate (Ritalin)
  • Dexmethylphenidate (Focalin)
  • Methamphetamine

[edit] Images

 *Sustained-Release 15mg Spansules:

 *Instant Release 30mg Adderall Tablets (mixture of D-amphetamine and L-amphetamine)

[edit] References

• Poison Information Monograph (PIM 178: Dexamphetamine Sulphate)
• Physician's 1991 Drug Handbook
• Dexamphetamine GPnotebook 1845887055
• Package inserts: New Zealand. Canada.

[edit] Footnotes