PHARMACOLOGY OF SOME STEREOISOMERS OF HYDROXYTROPANE DERIVATIVES OF PHENOTHIAZINE

¹ Pharmacology Section, Sterling-Winthrop Research Institute, Rensselaer, New York

The -and -isomers of hydroxytropane derivatives of phenothiazine have been compared with each other and with the parent tropane derivative.

The hydroxylated compounds were equal in activity and both were more active than the parent derivative in antagonizing the oxytocic effects of 5HT as measured by the isolated rat uterus preparation.

In the tests for central activity, where rate of metabolism and penetration of cellular barriers are more important, the -isomers were more active than their corresponding enantiomorphs. When compared with the parent tropane the -hydroxytropane had the same activity in potentiating hexobarbital and the a-hydroxytropane was more active; in the other tests for central activity the -isomer was similar to the parent compound and the -isomer was less active. It is suggested that this is due to differences in physico-chemical properties rather than to differences in affinities for any central effector sites.