Differential routes of cocaine administration indicate a peripheral cardiotoxic action

The present study utilized different routes of administration in unanesthetized Wistar Kyoto (WKY) rats to determine whether cocaine-induced death was mediated through a peripheral or central site of action. Administration of cocaine via a route that resulted in high concentrations of cocaine reaching the heart produced arrhythmias, convulsions, a decrease in heart rate and mean arterial pressure, and death. However, administration of the same dose via a route that resulted in passage of cocaine through the liver before reaching the heart produced only a pressor response. Additionally, administration of the same dose via a route that resulted in high levels of cocaine reaching the brain did produce a pressor response that was followed by a decrease in blood pressure and heart rate, arrhythmias, convulsions and death. However, these effects were delayed in comparison to the response when high concentrations of cocaine reached the heart immediately. These results support a peripheral site of action for cocaine-induced death.