Comparison of cocaine and Na+ channel blockers on cardio-respiratory function in the rabbit

The cardio-respiratory effects of cocaine were compared to various Na+ chan nel blocking Class I antiarrhythmics. Anesthetized rabbits were treated wit h various doses of either cocaine, quinidine, procainamide, lidocaine or fl ecainide. Cocaine produced clear decreases in blood pressure and heart rate . None of the other sodium channel blockers produced any change in blood pr essure, and heart rate was decreased only slightly by procainamide and lido caine. Cocaine produced larger increases in QRS duration than were observed for the four sodium channel blockers. All five drugs produced comparable i ncreases in respiratory rate. Separate rabbits were pretreated with either the alpha-adrenoceptor antagonist phentolamine or the beta-adrenoceptor ant agonist propranolol prior to cocaine. Phentolamine attenuated the blood pre ssure decrease following cocaine and propranolol attenuated the heart rate decrease following cocaine. These results suggest that the sodium channel b locking properties contribute only minimally to the overall effects of coca ine on blood pressure and heart rate. Further, the large effect of cocaine on QRS duration suggests that cocaine may act at sodium channels in a manne r different from the other drugs. This unique effect of cocaine may contrib ute to the sudden death associated with cocaine use in some individuals. (C ) 1999 Elsevier Science B.V. All rights reserved.