REMACEMIDE HYDROCHLORIDE AND ARL 15896AR LACK ABUSE POTENTIAL - ADDITIONAL DIFFERENCES FROM OTHER UNCOMPETITIVE NMDA ANTAGONISTS

This study was designed to determine the possible abuse liability and phencyclidine-like effects of the low-affinity uncompetitive N-methyl- D-aspartate (NMDA) antagonists remacemide hydrochloride )-2-amino-N-(1 -methyl-1,2-diphenylethyl)-acetamine hydrochloride] and ARL 15896AR [( +/-)-alpha-phenyl-2-pyridine-ethanamine dihydrochloride]. For the abus e-liability studies, in rats trained to self-administer cocaine intrav enously (0.1 mg/kg/injection), doses of remacemide HCl, ARL 15896AR, p hencyclidine, and saline were made available, and the number of inject ions self-administered was recorded. In different sets of rats, we ass essed the ability of these drugs to induce phencyclidine-like stereoty ped behavior. Doses of the compounds were expressed as multiples of th e 50% effective dose (ED(50)), as determined from the maximal electros hock (MES) test by using either oral or intravenous administration. No ne of the remacemide hydrochloride or ARL 15896AR doses was self-admin istered at a level higher than that of the saline vehicle, unlike coca ine and phencyclidine, which were self-administered at high and modera te levels, respectively. Unlike that with remacemide hydrochloride and ARL 15896AR, oral administration of the high-affinity uncompetitive N MDA receptor-antagonists phencyclidine, ARL 16247 [N-(3-ethylphenyl)-N -methyl-N'-naphthylguanidine] and MK-801 engendered phencyclidine-like stereotypy at doses near their MES ED(50) values. These data confirm the unusual safety of remacemide hydrochloride and ARL 15896AR and dem onstrate that they do not possess reinforcing properties. As such, the y are unlikely to present a drug-abuse problem in human beings.