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The effect of Dopram (doxapram hydrochloride, A. H. Robins Co.) on the pharmacologic responses to pentobarbital was evaluated. In naive and pentobarbital-tolerant mice, Dopram was shown to enhance significantly sodium pentobarbital-induced narcosis in a dose-related manner. The effect of the duration of action of Dopram on pentobarbital narcosis also was assessed. It was observed that Dopram (40 mg/kg, i.p.) significantly increased pentobarbital-induced narcosis even when administered 2 hr prior to challenge with sodium pentobarbital (60 mg/kg, i.p.) A significantly increased hypothermic response to sodium pentobarbital was seen in Dopram-treated animals. The half-life of pentobarbital in brain and serum was shown to be increased significantly in animals receiving Dopram, 40 mg/kg, i.p. The waking brain and serum pentobarbital concentrations were not significantly different in either group. These studies show that Dopram potentiates pentobarbital's effects. Further study is necessary to determine the sites of operation and mechanism of this potentiation.