Blockade of insulin release by certain phenothiazines

Chlorpromazine lowered the ratio of plasma insulin to blood glucose in adrenalectomized rats fed a glucose load. Desmethylchlorpromazine also lowered this ratio 30 min after glucose administration, but elevated it at 60 min. By contrast, fluphenazine had no significant effect on the ratio of plasma insulin to blood glucose. Chlorpromazine and desmethylchlorpromazine were more effective than fluphenazine in blocking insulin release from the isolated rat pancreas. Although adrenal epinephrine release and blockade of the effect of insulin may also be involved, the results of this study show that the hyperglycemic effect of certain phenothiazines is mainly determined by blockade of insulin release.