THE COMPETITIVE NMDA RECEPTOR ANTAGONIST SDZ-220-581 REVERSES HALOPERIDOL-INDUCED CATALEPSY IN RATS

The present studies investigated whether SDZ 220-581 oro-5-(phosphonom ethyl)[1,1'-biphenyl]-3-propanoic acid), a potent, competitive antagon ist at the NMDA glutamate receptor subtype, reversed haloperidol-induc ed catalepsy in rats, a widely used model of Parkinson's disease. SDZ 220-551 (0.32-3.2 mg/kg i.p.) dose- and time-dependently reduced the t ime spent in an abnormal position induced by haloperidol (1.0 mg/kg s. c.). Compared to other NMDA receptor antagonists the rank order of pot ency was MK-801 ,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) > S DZ 220-581 > SDZ EAA 494 (D-CPPene: 4-(3-phosphonoprop-2-enyl)-piperaz ine-2-carboxylic acid) > SDZ EAB 515 ino-5-(phosphonomethyl)[1,1'-biph enyl]-3-propanoic acid). Since it has been demonstrated that SDZ 220-5 81 counters the effects of L-dihydroxyphenylalanine (L-DOPA) on the mo tor disturbances of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP )-pre-treated primates, the results suggest that the reversal of halop eridol-induced catalepsy by competitive NMDA receptor antagonists may not be predictive of efficacy in other models of Parkinson's disease.