Effect of ammonium chloride on the potentiation of amphetamine by psychotropic drugs in the rat

Abstract

The effect of acidification of the urine on the potentiation of amphetamine by imipramine, butriptyline and chlorpromazine was investigated in the rat. Urine was acidified by administering ammonium chloride (500 mg/kg p.o.). Amphetamine, imipramine, butriptyline and chlorpromazine were injected i.p. CNS stimulation was measured in jiggle cages. Amphetamine and p-hydroxyamphetamine excretion in the urine were determined 4 hr after administration of the drugs. Ammonium chloride increased the rate of urinary excretion of amphetamine and shortened the intensity and the duration of amphetamine hypermotility. These findings correlated with lower levels of brain amphetamine. In rats treated with the combinations of amphetamine with (1) imipramine, (2) butriptyline and (3) chlorpromazine, ammonium chloride abolished the potentiation and prolongation of amphetamine effects. The effect of ammonium chloride on amphetamine excretion and brain levels in these groups was similar to that observed in animals treated with amphetamine alone. It is suggested that ammonium chloride blocked the potentiation of amphetamine stimulation by the psychotropic agents by promoting a more rapid excretion of amphetamine.