Regional distribution of imipramine, desipramine and specific [3H]desipramine binding sites in the rat brain after acute and chronic treatment of rats with imipramine has been investigated. Both substances were distributed unevenly within rat brain after single and prolonged administration of imipramine. This was partly connected with the regional cerebral blood flow, lipid content in the regions and lipophilicity of the substances investigated. It was also found that the number of specific [3H]desipramine binding sites was different in the various brain areas, and that prolonged administration of imipramine led to a decrease of their number in some of those regions. No correlation was found between the regional cerebral distribution of desipramine and the regional density of specific [3H]desipramine binding sites.

This study investigates how neuroleptics of phenothiazine or thioxanthene structure influence the pharmacokinetics of carbamazepine. Experiments were carried out on male Wistar rats. Carbamazepine and the neuroleptics were administered i.p., separately or together, for 2 weeks in the following daily doses (mg/kg): carbamazepine 15 during the 1st week of treatment and 20 during the 2nd week of treatment, promazine 10, chlorpromazine 2, perazine 10, chlorprothixene 2, flupenthixol 0.5. One hour after the last injection of carbamazepine and/or the neuroleptic, samples of blood plasma and brain were taken to determine the concentrations of carbamazepine and two of its metabolites: 10,11-epoxide and trans-10,11-diol. The neuroleptics increased the concentration of carbamazepine in plasma and in brain, but tended to decrease (with the exception of chlorpromazine) the concentration of the epoxide and increased the concentration of trans-10,11-diol. Metabolic in vitro studies did not show any significant differences between rats treated with carbamazepine alone and those treated with carbamazepine plus neuroleptic in the rates of the carbamazepine epoxidation, of 10,11-epoxide hydrolysis or of 1-naphthol glucuronidation.

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