PURINERGIC DRUGS AND CALCIUM-CHANNEL ANTAGONISTS ATTENUATE THE WITHDRAWAL SYNDROME FROM BARBITAL

The effects of some adenosine agonists and calcium channel antagonists on the induction of tolerance to and dependence on barbital in mice h ave been studied. The concurrent administration of barbital and one of the following adenosine agonists, D- or L-phenylisopropyl adenosine, cyclopentyl adenosine and chloroadenosine, or the adenosine antagonist s theophylline or 8-phenyltheophylline did not change the intensities of tolerance to and dependence on the barbiturate. N-ethylcarboxamide adenosine administered during the period of chronic administration of barbital significantly reduced the withdrawal syndrome. The administra tion of the calcium channel antagonists diltiazem, verapamil or nifedi pine was also ineffective in altering the processes of tolerance and p hysical dependence when given concomitantly with barbital. Abstinence behavior was significantly reduced when mice were treated during the f irst 48 h of withdrawal from the barbiturate with either L-phenylisopr opyl adenosine, N-ethylcarboxamide adenosine, nifedipine or verapamil. These results are discussed in relation to the attenuation of toleran ce to and dependence on benzodiazepines induced by similar treatments.