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+ channel blocking Class I antiarrhythmics. Anesthetized rabbits were treated with various doses of either cocaine, quinidine, procainamide, lidocaine or flecainide. Cocaine produced clear decreases in blood pressure and heart rate. None of the other sodium channel blockers produced any change in blood pressure, and heart rate was decreased only slightly by procainamide and lidocaine. Cocaine produced larger increases in QRS duration than were observed for the four sodium channel blockers. All five drugs produced comparable increases in respiratory rate. Separate rabbits were pretreated with either the alpha-adrenoceptor antagonist phentolamine or the beta-adrenoceptor antagonist propranolol prior to cocaine. Phentolamine attenuated the blood pressure decrease following cocaine and propranolol attenuated the heart rate decrease following cocaine. These results suggest that the sodium channel blocking properties contribute only minimally to the overall effects of cocaine 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 manner different from the other drugs. This unique effect of cocaine may contribute to the sudden death associated with cocaine use in some individuals.
Erzouki
H K
HK
Preclinical Pharmacology Section, Behavioral Neurosciences Branch, NIH/NIDA Intramural Research Program, Baltimore, MD 21224, USA.
Goldberg
S R
SR
Schindler
C W
CW
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005424:Flecainide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011342:Procainamide; D011802:Quinidine / Q000494:pharmacology; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*; D026941:Sodium Channel Blockers
D000889:Anti-Arrhythmia Agents; D018765:Dopamine Uptake Inhibitors; D026941:Sodium Channel Blockers; D008012:Lidocaine; D003042:Cocaine; D011802:Quinidine; D005424:Flecainide; D011342:Procainamide