Dextroamphetamine
3 sources
Mechanism of action
The exact mechanism of amphetamines as a class is not known. Dextroamphetamine acts by preventing reuptake, increasing release, and stimulating reverse-transport of dopamine in synaptic clefts in the striatum. Newer evidence shows amphetamines may also alter the number of dopamine transporters in synaptic clefts.
Pharmacodynamics
Dextroamphetamine is a noncatecholamine, sympathomimetic amine that acts as a CNS stimulant. Dextroamphetamine raises systolic and diastolic blood pressure, acts as a weak bronchodilator, and also acts as a respiratory stimulant. The general mechanism of action of dextroamphetamine has not been well established.
Pharmacokinetics
Half-life
11.75 hours. In a study of post-stroke patients the half life was 16.0 hours in females and 12.4 hours in males. Studies in healthy populations show a half life of 7.9 hours.
The half-life was 11.75 hours, /for the ingestion of 10 mg of dextroamphetamine sulfate in oral solution form by healthy volunteers..../
... The (+)-amphetamine isomer is more rapidly metabolized than the (-)-isomer, & under alkaline conditions, the (+)-isomer elimination half-life is significantly shorter (17.0 hr vs 12.7 hr). Under acidic urine conditions, renal excretion is the major route of elimination & thus the difference in isomer half-life is minimized.
Absorption
Bioavailability data of dextroamphetamine is not readily available, however there is no difference in bioavailability when taken with or without a meal.
A third of the drug is eliminated renally.
195L.
17L/h.
Amphetamines are readily absorbed from the GI tract and effects persist for 4-24 hours. Amphetamines are distributed into most body tissues with high concentrations occurring in the brain and cerebral spinal fluid (CSF). Amphetamine appears in the urine within about 3 hours following oral administration. Urinary excretion of the amphetamines is pH-dependent and excretion is enhanced in acidic urine. Following oral administration of racemic amphetamine to humans, approximately equal amounts of both isomers were excreted during the first 12 hours; after the first 12 hours, a continually decreasing proportion of the d-isomer was excreted. Following oral administration of a 70-mg radiolabeled dose of lisdexamfetamine (a prodrug of dextroamphetamine), 96% of the dose was recovered in the urine; of the recovered radioactivity, 42% of the dose was related to amphetamine, 25% to hippuric acid, and 2% to the parent drug. Dextroamphetamine and levamfetamine (no longer commercially available in the US) appear to have different metabolic fates, but the relationship between the fate of the drugs and their pharmacologic activity has not been determined. There are some data to indicate stereospecific metabolism of amphetamine and its isomers, but stereospecific urinary excretion appears unlikely.
Ingestion of 10 mg of dextroamphetamine sulfate in oral solution form by healthy volunteers produced an average peak dextroamphetamine blood level of 33.2 ng/mL. The half-life was 11.75 hours. The average urinary recovery was 38% in 48 hours.
Metabolism
Dextroamphetamine is metabolized by cytochrome P-450 2D6 in the liver to 4-hydroxyamphetamine and later conjugated by sulfotransferase or glucoronyltransferase.
Yields N-acetylamphetamine in rabbit. Benzyl methyl ketoxime in rabbit & guinea pig. /From table/
Yields p-hydroxy-d-amphetamine in rat & dog. /From table/
Amphetamine is a noncatechol, sympathomimetic amine and has a greater CNS stimulant activity than epinephrine and other catecholamines. Lisdexamfetamine dimesylate is a prodrug and has little, if any, pharmacologic activity until converted to dextroamphetamine by first-pass intestinal and/or hepatic metabolism. Inactivation of sympathomimetic noncatecholamines largely depends on breakdown by monoamine oxidase and since substitution of an alkyl group for hydrogen on the a-carbon atom blocks enzymatic inactivation of the amino group, the duration of action of noncatecholamines (but not of catecholamines, which are inactivated largely by a different mechanism) is prolonged by a-substitution. The absence of a hydroxyl group on the aromatic ring of amphetamine reduces inactivation of the drug in the GI tract and the amphetamines are active following oral administration.
Yields N-methyl-d-amphetamine in rabbit. Alpha-methyl-beta-phenethylhydroxylamine in rabbit. /From table/
Yields d-norephedrine in man, in beef; phenylacetone in rabbit, man & dog. /From table/
External links
Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.