Effect of neuroleptics on indoleamine-N-methyltransferase activity and brain metabolism of bufotenin

Gomes U.C.R. ; McCarthy B.W. ; Shanley B.C. (1981)


A range of neuroleptics, non-neuroleptic phenothiazines and antidepressants were tested for their ability to inhibit purified rabbit lung indoleamine-N-methyltransferase (INMT) and to modify the metabolism of [3H]bufotenin administered intraventricularly. Benperidol and droperidol proved to be the most potent inhibitors of INMT among the compounds tested. On the other hand trifluperidol and haloperidol showed no inhibitory activity at concentrations up to 2.5 mM, while chlorpromazine, thioridazine, pericyazine and perphenazine were effective only at 250 μM or 2.5 mM. Oxidative deamination was shown to be an important pathway in normal rat brain for the metabolism of bufotenin. Of the drugs tested only chlorpromazine elevated the brain [3H]bufotenin/[3H]-5-HIAA ratio whereas pimozide and thiothixene caused a decrease. These findings suggest that neuroleptic drugs in general do not exert their anti-psychotic effects by inhibiting the synthesis or accelerating the oxidative deamination of N,N-dimethylated indoleamines.

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