ADENOSINE 3',5'-MONOPHOSPHATE IN GUINEA PIG CEREBRAL CORTICAL SLICES: EFFECT OF BENZODIAZEPINES

Several benzodiazepines, diazepam, chlordiazepoxide, desmethyldiazepam, methyloxazepam and oxazepam, potentiate the accumulation of cyclic AMP elicited by histamine and histamine: noradrenaline in cerebral cortical slices of guinea pig. In addition, these drugs increase basal levels of cyclic AMP by about 100 per cent. When adenosine is used to stimulate cyclic AMP formation only diazepam, desmethyldiazepam and methyloxazepam are increasing cyclic AMP levels significantly over respective controls. The order of potency is: diazepam > desmethyldiazepam > methyloxazepam > oxazepam > chlordiazepoxide. Diazepam decreases the rate of degradation of cyclic AMP after removal of the stimulatory agents (histamine : noradrenaline). Dose response curves for diazepam under two stimulatory conditions are shown. A significant effect is obtained at 50 μm -diazepam and an ED₅₀ of 40 μm is calculated with histamine as the stimulatory agent. When cyclic AMP formation is elicited by histamine : noradrenaline a significant effect of diazepam is seen at 10 μm and an ED₅₀ of 16 μm is obtained. These results lend support to the hypothesis that the psychotropic action of the benzodiazepines may, at least in part, involve the cyclic AMP generating systems of the central nervous system.