NMDA receptor antagonist effects of the stereoisomers of beta-cyclazocine in rats, in vivo and in vitro.
(+)- and (-)-beta-cyclazocine were examined as NMDA receptor antagonists following bath application to rat cortical wedges in vitro and i.v. administration to rat spinal cord neurones in vivo. Both isomers were found to be selective NMDA antagonists with little effect on excitations evoked by quisqualate. In vitro, IC50 values for (-)- and (+)-beta-cyclazocine against responses to 40 microM NMDA were estimated at 0.51 and greater than 100 microM, respectively. In vivo, (-)-beta-cyclazocine 0.25 mg.kg-1 reduced NMDA-evoked excitations by 70%, an effect substantially greater than that produced by (+)-beta-cyclazocine 2.5 mg.kg-1. (-)-beta-cyclazocine is the most potent NMDA antagonist benzomorphan tested to date, being about twice as potent as (-)-alpha-cyclazocine in this respect. In addition, the separation in potency exhibited by the beta-cyclazocine enantiomers as NMDA antagonists is much greater than that reported previously for the stereoisomers of the alpha-series.
Church
J
J
Department of Physiology, University of British Columbia, Vancouver, Canada.
Millar
J D
JD
Jones
M G
MG
Lodge
D
D
D000818:Animals; D003496:Cyclazocine / Q000494:pharmacology*; D066298:In Vitro Techniques; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D017478:Receptors, Phencyclidine; D013237:Stereoisomerism
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D010622:Phencyclidine; D003496:Cyclazocine