Amfetamine metabolism

Tranylcypromine is a non-hydrazine monoamine oxidase (MAO) inhibitor with actions and uses similar to those of phenelzine, but with less prolonged inhibition. Its half-life is 90-190 minutes. It is structurally related to amfetamine, to which it is metabolized in overdose (1). 

Monoamine oxidase inhibitors (MAOI) are not completely selective for MAO and impair the metabolism of tricyclic antidepressants, of some sympathomimetics, e.g. phenylpropanolamine, amfetamine, of opioid analgesics, especially pethidine, and of mercaptopurine. 

Fenproporex, one of the lesser known anorectic drugs, is structurally related to amfetamine, to which it is rapidly metabolized after oral ingestion. Stimulatory effects, somnolence, and electroencephalographic abnormalities are reported to be the major undesired reactions (1). 

As recreational use of ecstasy has dramatically increased in recent years, deaths related to its use have been reported. In a retrospective review of all violent deaths from 1992 to 1997 in South Australia, six deaths were associated with ecstasy abuse aU occurred after September 1995. Three victims had documented hyperthermia and there was evidence of hyperthermia in another. The authors suggested that individual susceptibility to MDMA may be caused by impaired metabolism by CYP2D6 or through genetically poor metabolism (seen in 5-9% of Caucasians). One woman, who died with a cerebral hemorrhage, had fluoxetine (a CYP2D6 inhibitor) present in her blood. Furthermore, toxicology identified paramethoxyamfetamine (PMA) in all the cases, amfetamine/metamfetamine in four cases, and... 

Selegiline is metabolized to amfetamine and metamfetamine, and can therefore cause insomnia (SEDA-17,167). 

Ecstasy (MDMA methylenedioxymethamfetamine). For comments on the effects of SSRIs on the metabolism of ecstasy and the possibility of increased serotonin effects, see Amfetamines and related drugs + SSMs ,... 

Selegeline, a monoamine oxidase inhibitor, is dealkylated by metabolism to amfetamine. The R isomer forms R amfetamine which has little effect on the CNS whereas the S isomer forms S amfetamine which has strong CNS effects. The drug is given as the pure R isomer. 

---