Influence of neuroleptics on pharmacokinetic parameters of amphetamine in rat after single and double injections

Abstract

Sprague-Dawley rats (90-1 00 g) were injected i.p. with saline, iprindole (1 0 mg/kg), clozapine (10 mg/kg), pimozide (10 mglkg), or molindone (10 mg/kg), and 30 min later with de~tro-~H-amphetamine (5 mg/kg). For two dose studies, a second injection of 3H-amphetamine (5 mgikg) was administered 3 hr after the first dose in saline or iprindole pretreated rats. In both studies, brain and hepatic levels of amphetamine paralleled the plasma levels, were highest at 1 hr in single dose and at 4 hr in two dose study, and thereafter, started declining. lprindole markedly increased tissue amphetamine levels in single dose experiments and further raised and prolonged them up to 24 hr in two dose experiments. Both pimozide and molindone significantly enhanced amphetamine levels, and this effect lasted for 1 and 3 hr, respectively (single dose study); clozapine was ineffective. From the data, it appears that several chemically unrelated neuroleptics alter the distribution and elimination of amphetamine; such alterations need to be assessed in clinical situations, since neuroleptics are used in amphetamine intoxication.