EFFECTS OF CHLORPROMAZINE AND HALOPERIDOL ON THE DISPOSITION OF MESCALINE-¹⁴C IN MICE

¹ Ensor Research Laboratory, William S. Hall Psychiatric Institute, Columbia, South Carolina

Chlorpromazine (CPZ)(15 mg/kg) as well as haloperidol (10 mg/kg) when injected 45 minutes after 50 mg/kg (2 µc) of mescaline effectively blocked mescaline-induced altered behavior within 7 to 10 minutes. In a reverse situation, mescaline (50, 100 or 300 mg/kg) administered 30 minutes after CPZ or haloperidol did not alter tranquilizing effects of the latter drugs. Pre- and post-treatment with CPZ resulted in marked prolongation of disappearance of mescaline in all organs examined; at 3 hours, tissue levels were 3 to 7 times more than controls. Haloperidol had no effect on mescaline disappearance. In controls, brain mescaline contents at 1, 2 and 3 hours were 200 ± 25, 134 ± 29 and 71 ± 8 ng/g. In animals pretreated with CPZ, the levels of mescaline were the same as controls at 1 hour but were markedly elevated at 2 and 3 hours (165 and 310%, respectively). This deviation persisted for at least 6 hours. CPZ-induced effects might be due to interference with metabolic processes necessary for maintenance of cell membrane permeability and/or with urinary excretion of mescaline. Although CPZ blocked mescaline-induced altered behavior, its apparent effect on the disposition of mescaline may be of significance from the standpoint of drug interaction.