Effects of cocaine and its quaternary derivative cocaine methiodide on cardiovascular function in squirrel monkeys

The effects of cocaine and its quaternary derivative cocaine methiodide, which does not cross the blood-brain barrier, were studied on cardiovascular function in squirrel monkeys. In conscious monkeys, cocaine produced clear dose-dependent increases in blood pressure and heart rate, while cocaine methiodide did not. Both cocaine and cocaine methiodide enhanced the effects of norepinephrine in anesthetized animals, suggesting that both inhibit neuronal uptake of norepinephrine; cocaine was approximately 30 times more potent than cocaine methiodide. In anesthetized monkeys both cocaine and cocaine methiodide produced small, short duration pressor effects, although cocaine was at least 10 times more potent than cocaine methiodide. Cocaine's effects in anesthetized animals were clearly blunted in comparison to its effects in conscious animals. These effects of cocaine on blood pressure occurred at doses lower than those required to enhance norepinephrine's effects, indicating that the norepinephrine uptake blocking effects of the drugs cannot fully account for their cardiovascular effects. The greatly enhanced effect of cocaine in conscious animals and the finding that cocaine methiodide had little effect in conscious animals indicates that central mechanisms are involved in the effects of cocaine on cardiovascular function in conscious animals.