Dissociation of the cytotoxicity of cocaine from its local anaesthetic effect: A comparison with lidocaine.
It has been suggested that cocaine may be directly toxic to myocardial cells. The mechanism of the toxicity is not known. Because we found that cocaine and lidocaine shared similar patterns of cytotoxicity, a role for local anaesthesia in the cytotoxicity of cocaine was evaluated in cultured rat cardiomyocytes. The cells were incubated with cocaine or lidocaine at different concentrations for up to 48 hr. At equal molarities, cocaine and lidocaine showed similar patterns of toxicity as assessed by leakage of lactate dehydrogenase (LDH) into cell medium and by cell viability staining with propidium iodide (PI). Increased extracellular sodium (Na(+)) ameliorated lidocaine-induced LDH release, but had no effect on cocaine-treated cultures. The addition of veratridine, an activator of Na(+) channels, did not change the toxicity of both drugs. Isoproterenol did not affect cocaine-induced LDH leakage, whereas it significantly potentiated lidocaine toxicity. These data suggest that the local anaesthetic action of cocaine may not contribute to its cytotoxicity to myocardial cells.
Yuan
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Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, TX 78712, USA.
Acosta
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