EFFECT OF DIACETYLMONOXIME ON THE ACTION OF CONVULSANT AND SEDATIVE-HYPNOTIC BARBITURATES

¹ Department of Pharmacology, Stanford University School of Medicine, Palo Alto, California

Mice and rats pretreated with DAM lose their righting reflex when given 3,5 dimethyl-butylethylbarbiturate (DMBEB) in doses of 25 to 35 mg/kg. Although these doses of DMBEB cause motor convulsions and death in control (saline injected) animals, DAM treated animals do not exhibit motor convulsions nor do they die. Pretreatment with DAM was also shown to prolong barbiturate induced loss of righting reflex (RR) in mice, rats and rabbits. DAM failed to inhibit the metabolism of either hexobarbital or DMBEB by liver microsomes in vitro. In addition, when mice or rats were injected with DAM on awaking from a barbitu-rate-induced sleep, these animals again lost their righting reflex; studies in mice with C¹⁴-labeled pentobarbital showed that under these conditions DAM did not elevate the brain barbiturate level through a redistribution of the drug within the body.

Since DAM does not inhibit barbiturate metabolism or effect a redistribution of barbitu-rate within the body, it is concluded that prolongation of RR is brought about either by a direct central action of DAM or by barbiturate potentiation of the weak neuromuscular blocking action of this oxime. Whether the anticonvulsant properties of DAM can be associated with the ability of DAM to prolong the action of sedative hypnotic barbiturates cannot be discerned from the data presented in this report.