Title: A comparison of the effects of chlorpromazine, 7-hydroxychlorpromazine and chlorpromazine sulfoxide on the activity of central dopaminergic neurons
Abstract: Using single unit recording techniques, chlorpromazine and two of its naturally occuring metabolites in man, 7-hydroxychlorpromazine and chlorpromazine sulfoxide, were tested for their ability to reverse amphetamine-induced depression of rat dopaminergic ventral tegmental neurons (A10). Small equivalent doses of chlorpromazine and 7-hydroxychlorpromazine were found to readily reverse amphetamine-induced depression of these cells. Chlorpromazine sulfoxide was found to be 50–100 times less potent in this regard. Previous findings have demonstrated that only phenothiazines with antipsychotic properties reverse amphetamine-induced depression of A10 neurons. Thus, we would predict that 7-hydroxychlorpromazine would have anti-psychotic properties whereas chlorpromazine sulfoxide would not. A preliminary study by Sakalis et al., suggests that plasma levels of chlorpromazine and 7-hydroxychlorpromazine are possibly correlated with the therapeutic effects of chlorpromazine in schizophrenia. Chlorpromazine sulfoxide levels, on the other hand, are reported to be high in chlorpromazine treated non-responders. Thus there is a direct parallel between predictions of antipsychotic efficacy based on our test model and the possible clinical importance of these chlorpromazine metabolites. Both findings suggest that 7-hydroxychlopromazine might be a good antipsychotic agent.
Publication Year: 1974
Publication Date: 1974-07-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 28
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