STRYCHNINE-INSENSITIVE GLYCINE SITE ANTAGONISTS ATTENUATE A CARDIAC ARREST-INDUCED MOVEMENT DISORDER

Male Sprague-Dawley rats underwent experimentally induced cardiac arre st and resuscitation, subsequently exhibiting involuntary jerking move ments (myoclonus) with salient features similar to the human form of t he disorder. The novel strychnine-insensitive glycine site antagonists ACEA-1011 romethyl-1,2,3,4-tetrahydroquinoxaline-2,3,-dione) and ACEA -1021 (5-nitro-6,7-dichloro-quinoxalinedione) significantly attenuated the myoclonus in cardiac-arrested rats. (+)-HA-966, (+/-)-HA-966 (3-a mino-1-hydroxy-2-pyrrolidinone), and felbamate (2-phenyl-1,3-propanedi ol dicarbamate) were also effective. Although the drugs vary in their selectivity for strychnine-insensitive glycine sites, they all possess antagonist activity at these sites. Vehicle injections (saline, dimet hyl sulfoxide, water) were without effect and no obvious side effects were observed with any of the ligands tested in this study. Since hype rexcitability in the central nervous system is thought to underlie myo clonus, the attenuation of excitatory amino acid neurotransmission thr ough antagonism of strychnine-insensitive glycine sites provides a log ical mechanism of action for the antimyoclonic effects observed herein .