Abstract
Chlorpromazine and 10 of its mono- and disubstituted metabolites were investigated for their effects on the CNS of male rats and mice. All of the compounds decreased motor activity and respiration, and all but two of the compounds decreased heart rate in rats. The most potent metabolite in depressing spontaneous motor activity of mice was 3,7-dihydroxychlorpromazine, with an ED50 of 5.1 mg./kg. i.p. in comparison to chlorpromazine which had an ED50 of 2.0 mg./kg. i.p. However, the 3,7-dihydroxy derivative was approximately twice as toxic as chlorpromazine in mice. 7,8-Dihydroxychlorpromazine did not alter forced motor activity, but it did induce a dose-related depression of spontaneous motor activity; 7-hydroxy-8-methoxy derivative also produced a marked decrease in spontaneous motor activity with minimal effects on forced motor activity. None of the compounds demonstrated anticonvulsant activity, and only 7-hydroxy-chlorpromazine elicited effects suggesting possible antidepressant activity. Barbiturate sleeping time was potentiated by all of the compounds, mainly due to their CNS depressant properties.
Published Version
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