Excitatory amino acid receptor antagonists: Potential implications for cardiovascular therapy and cocaine intoxication

Abstract

A hypothesis is offered which suggests that excitatory amino acid (EAA) receptor antagonists have a potential role in the management of cardiac and cardiovascular pathophysiology resulting from increased central autonomic discharge. This suggestion is based on evidence that endogenous EAA release occurs following cerebral hypoxic insults, that cerebral hypoxia is associated with a high incidence of circulatory damage and that local intracerebral injection of EAA receptor agonists stimulates cardiovascular function and causes cardiac necrosis. Clinical events that can be linked to cerebral hypoxia, EAA release and production of cardiac pathology include intracerebral hemorrhage, cerebral trauma and stress. Cocaine intoxication may also involve central EAA release and experimental data are presented which demonstrate that pre-treatment with the EAA receptor antagonist, MK-801, can antagonize cocaine toxicity in the conscious rat. Antagonists at EAA receptors may be clinically useful in the management of disease states where heart-brain interactions contribute to morbidity and mortality.