Influence of intracerebroventricular injections of N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphate on sodium pentobarbital-induced narcosis in rats.

Premedication with dibutyryl cyclic AMP (225 μg, i.c.v.) decreased the responsiveness of the central nervous system and lethality to sodium pentobarbital in the rat. The LD₅₀ of sodium pentobarbital was increased (79.9–116 $\text{solmg}\text{kg}$ i.p.) and the sleep time was decreased from 120min to 76 min in dibutyryl cyclic AMP pretreated animals. The brain and plasma pentobarbital concentrations at the time of awakening were higher in the dibutyryl cyclic AMP group as compared to saline pretreated rats. The threshold dose level of sodium pentobarbital as determined from the dose—response curves and the dose of intravenous infused pentobarbital necessary to suppress EEG activity was increased after administration of the cyclic nucleotide. Pretreatment with gradient doses of dibutyryl cyclic AMP produced a biphasic dose-response of pentobarbital sleep time with the shortest duration observed at 225 μg of dibutyryl cyclic AMP and a progressive increase in duration of sleep time from 250 and 275 μg was produced. Doses of dibutyryl cyclic AMP greater than 275 μg produced death in all animals. The cardiovascular depressant action of pentobarbital was antagonized by dibutyryl cyclic AMP. However, the hypothermic action of pentobarbital was not reversed. The results suggest dibutyryl cyclic AMP produces a generalized stimulation of the CNS and does not specifically antagonize barbiturate-induced toxicity.