General Pharmacology of Amphetamine-Like Drugs

Abstract

Amphetamine and related central stimulant drugs are derivatives of ß-phenylethylamine (Table 1) and are thus relatively simple organic bases. The general ßphenylethylamine skeleton is one which amphetamine shares with the neurotransmitters noradrenaline, adrenaline, and dopamine. Phenylethylamine itselfhas central stimulant properties, but has an extremely short half-life in the body due to rapid metabolism by monoamine oxidase (MAO). Amphetamine has, due to steric hindrance by the ex-methyl group, much less affinity for MAO and therefore has a longer half-Iife.Most amphetamines have cardiovascular, psychomotor stimulant, hyperthermic, and anorexigenic actions. All of the structural features of amphetamine are important far its spectrum of pharmacologic activity. Any alteration may enhance, diminish, or attenuate one or several components in the actions of the parent drug. (1) Substitution of the phenyl ring, (2) alteration of the length of the side chain, (3) substitution on the primary nitrogen group, (4) substitution of the ex-and ß-carbon atoms, and (5) their absolute configuration have been studied and will be briefly discussed here. For a more thorough review on the subject the reader is referred to the papers by BIEL (1970), vANRossuM and SIMONS (1969) and VREE (1973. The effect of ring and side-chain substitution on distribution and elimination of the amphetamines has been discussed by BECKETT and BROOKES (1970). recently reviewed the biochemical pharmacology of the amphetamines. The metabolism and disposition of methylphenidate were reported by F ARAJ et al.