Deuterated Halothane???Anesthetic Potency, Anticonvulsant Activity, and Effect on Cerebellar Cyclic Guanosine 3???, 5???-Monophosphate

Abstract

The effect of substituting deuterium for hydrogen in the halothane molecule on anesthetic potency, motor activity, and cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) content was studied in mice. The concentration of halothane required to abolish the righting reflex in 50% of the mice (ED50RR) was chosen as index of anesthetic potency; cerebellar control of motor activity was evaluated by the incidence of isoniazid-induced convulsions. The ED50RR for deuterated (D)-halothane was similar to that of halothane (0.87 +/- 0.04 and 0.88 +/- 0.03 vol%, respectively). Both D-halothane and halothane (0.15-0.90 vol%) protected the mice against isoniazid-induced convulsions and decreased cerebellar cGMP content in a dose-dependent manner. D-halothane and halothane were equipotent on both parameters. Thus deuteration did not alter the anesthetic potency, the anticonvulsant activity, or the effect on cerebellar cGMP content of the anesthetic. Furthermore, the reactivity of the C-H bond is probably not critical for these actions of halothane.