ALPHA(2) ADRENERGIC AGONISTS PREVENT MK-801 NEUROTOXICITY

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate re ceptor are of considerable interest for various neurotherapeutic purpo ses, including preventing neuronal degeneration in stroke and CNS trau ma, suppressing neuropathic pain and preventing the development of tol erance to opiate analgesics. Unfortunately, NMDA antagonists can cause potentially serious side effects, including acute neurodegenerative c hanges in corticolimbic regions of the adult rat brain and psychotic r eactions in adult humans. We have been investigating the mechanisms un derlying the neuropathological changes in vat brain and exploring meth ods of suppressing or preventing such changes. Here we report that alp ha(2) adrenergic agonists can prevent NMDA antagonist neurotoxicity. T herefore, administering at adrenergic agonists together with NMDA anta gonists may be a valuable strategy for preventing adverse side effects of NMDA antagonists and making these agents safer for various neuroth erapeutic purposes.