These studies demonstrated that 5-ethyl-5-(3-hydroxyl-1-methyl-butyl)-barbituric acid (PB-OH), a major metabolite of pentobarbital, antagonized pentobarbital-induced narcosis in both naive and pentobarbital tolerant mice. In PB-OH pretreated mice, the sleeping time induced by sodium pentobarbital was significantly shorter than that of the saline control animals. However, PB-OH failed to modify the pentobarbital-induced hypothermia. The findings also demonstrated that hepatic microsomal enzyme activity and half lives of pentobarbital and PB-OH in both plasma and brain were not modified by the pretreatment of PB-OH. The specific antagonistic effect of PB-OH appears to be a direct effect on sites in the CNS.
Bibliographical noteFunding Information:
These studies were supported by NIDA grant DA-01403 . H . H . Loh is a recipient of a NIMH Research Scientist Development Award, K2-DA-70554 . The authors wish to thank Mrs . Susan Culbertson for assistance in preparation of the manuscript and Dr . Mary E . Davis for many helpful suggestions .