Treatment advances for cocaine-induced ischemic stroke: Focus on dihydropyridine-class calcium channel antagonists

Objective: The authors reviewed the pathogenesis of cocaine-related cerebra l ischemia, appraised current knowledge of its sequelae, and assessed the r ole of putative therapeutic agents, particularly dihydropyridine-class calc ium channel antagonists, Method: The authors per-formed an OVID-based literature review of all index ed journals between 1966 and 2000. Results: Cocaine abuse significantly increases the risk of ischemic stroke. The principal mechanism of cocaine-induced cerebral ischemia is vasospasm of large cranial arteries or within the cortical microvasculature. increase d levels of extracellular monoamines, particularly dopamine, mediate vasosp asm. Neuroanatomical and labeling studies also have shown that dopamine-inn ervated neurons may regulate cerebral blood flow. Indeed, dopamine-rich bra in regions appear to be relatively specific targets for cocaine-induced cer ebral ischemia. Neuroimaging studies show that cocaine-induced hypoperfusio n can persist even after 6 months of abstinence. Hypoperfusion can result i n deficits on complex and simple psychomotor tasks but perhaps not on memor y or attention. Severe cerebral ischemia can directly precipitate neuronal death and degradation, a condition exacerbated by liberation of the excitat ory amino acid glutamate. Dihydropyridine-class calcium channel antagonists inhibit cocaine-mediated dopamine release on neurons involved in vasospasm and the control of cortical circulation. Other causes of cerebral ischemia include thrombogenesis and vasculitis. Although antithrombotic agents have potential in alleviating cocaine's neurotoxic effects, their use may be li mited by the risk of spontaneous hemorrhage, Conclusions: Cocaine abuse can result in stroke, neuroischemia, and cogniti ve deficits that can persist even after prolonged abstinence. Dihydropyridi ne-class calcium channel antagonists, such as isradipine, show promise as t herapeutic agents for preventing cocaine-induced cerebral ischemia.