Studies on Accumulation of (14C)-Mescaline in Brain Homogenates: Effects of Psychotropic and Other Agents

Mescaline accumulates in the pellet fraction when incubated with rat brain homogenates. High concentrations (1.33 µmol/ml) of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline, and amitriptyline inhibit this accumulation, with tricyclic antidepressants less potent than tranquilizers. Lower concentrations (0.133–0.44 µmol/ml) are less effective. The drugs do not alter mescaline metabolism, as the ratio of its metabolite TMPA to mescaline remains unchanged. The inhibition of mescaline accumulation by high tranquilizer concentrations may divert more hallucinogen to receptor sites, offering an explanation for why tranquilizers worsen clinical syndromes of hallucinogenic poisoning.

Study at a glance

Abstract

Incubation of rat brain homogenates or 14,500 g pellet isolated from the homogenate with (14C)-mescaline was associated with accumulation of (14C)-mescaline in the pellet. 1.33 mumol/ml of chlorpromazine, trifluoperazine, fluphenazine, imipramine, desmethylimipramine, nortriptyline and amitriptyline inhibited the accumulation of mescaline. Lower concentrations (0.133-0.44 mumol/ml) of the psychotropic drugs were less effective. The tricyclic antidepressants were less potent than the tranquilizers. Although the trimethoxyphenylacetic acid (TMPA) levels of the pellet were also reduced by the psychotropic drugs, the TMPA:mescaline ratios were unchanged indicating that the drugs had no effect on the metabolism of mescaline. The inhibition of accumulation of mescaline by the high concentrations of tranquilizers may divert more of the hallucinogen to the receptor site. Thus, an explanation for the reported worsening of clinical syndrome of hallucinogenic poisoning by tranquilizers is provided.