Effects of various neuroleptics, phenobarbital and SKF 525-A on dimethyltryptamine content in rat brain and liver

The content of N,N-dimethyltryptamine (DMT) in the brain and liver of adult male Holtzman rats was determined after different pretreatment times with various drugs. The agents used for pretreatment were given i.p., unless otherwise specified on a mg/kg free base calculation and were as follows: chlorpromazine (0.032 to 18), haloperidol (0.1 to 3.2), thiothixene (0.1 to 3.2), octoclothepin (0.1 to 3.2), methiothepin (0.1 to 3.2), molindone (0.1 to 10.0), phenobarbital (45-90 as salt) and SKF 525-A (100 as salt). The chronic effects of chlorpromazine and phenobarbital on DMT levels were also studied in the rat. The drug dose of nonlabeled cold DMT was either 3.2 or 10.0 mg/kg as free base, while the dose of radioactive side chain-1-DMT was 3.14 mg/kg as free base. Cold DMT was assayed spectrophotofluorometrically while radioactive DMT and its acid metabolites were measured by a liquid scintillation counter. Neuroleptics varied markedly in their ability to alter DMT content. Octoclothepin was > haloperidol > methiothepin in reducing brain DMT content while chlorpromazine and molindone increased it. In contrast, chlorpromazine was > haloperidol > molindone > methiothepin in elevating DMT liver content while methiothepin and octoclothepin had biphasic effects in the liver. In general, the indoleacetic acid level was not markedly affected. Chronic phenobarbital lowered brain DMT and SKF 525-A pretreatment elevated brain and liver DMT levels.