Cocaine-induced cardiovascular effects: Lack of evidence for a central nervous system site of action based on hemodynamic studies with cocaine methiodide

It has been suggested that cocaine acts directly in the brain to enhance ce ntral sympathetic outflow. However, some studies suggested that the cardiov ascular effects of cocaine are related to a peripheral action. To character ize further the site of cocaine's cardiovascular effect, we compared the he modynamic effects of cocaine (2 mg/kg, i.v. bolus) with those observed afte r administration of an equimolar dose (2.62 mg/kg, i.v. bolus) of cocaine m ethiodide, a quaternary derivative of cocaine that does not penetrate the b lood-brain barrier, by using sufentanil-sedated dogs. Cocaine produced sign ificant (p < 0.05) increases in heart rate (+37 +/- 11 beats/min), mean art erial pressure (+55 +/- 11 mm Hg), left ventricular end-diastolic pressure (+5.3 +/- 1.0 mm Hg), and cardiac output (+2.4 +/- 0.9 L/min). Cocaine meth iodide produced increases in heart rate (+57 +/- 11 beats/min), mean arteri al pressure (+45 +/- 11 mm Hg), left ventricular end-diastolic pressure (+3 .4 +/- 1.0 mm Hg), and cardiac output (1.1 +/- 0.9 L/min), which were not s ignificantly different from those observed with cocaine. Because opiate sed ation potentially might have attenuated central sympathetic outflow we furt her confirmed the qualitative similarity of the actions of cocaine and coca ine methiodide on heart rate and blood pressure in unsedated, conscious dog s. Our data suggest that the cardiovascular effects of cocaine result prima rily from a peripheral site of action.