Cyclazocine and pentazocine as N-methylaspartate antagonists on cat and rat spinal neurons in vivo.

The effects of the racemic mixtures and separated enantiomers of cyclazocine and pentazocine were examined on the responses of spinal neurons to excitatory amino acid analogs and acetylcholine in pentobarbital-anesthetized cats and rats. Each compound was administered both by microelectrophoresis and by i.v. injection. The racemic mixture and separated optical isomers of cyclazocine reduced selectively neuronal excitations evoked by N-methylaspartate (NMA), with only small and variable effects on responses to quisqualate and kainate. (+/-), (+)- and (-)-pentazocine also antagonized NMA actions, although they were less potent and somewhat less selective than the corresponding cyclazocine compounds in this respect. Overall, in both microelectrophoretic and i.v. tests, (+/-)-cyclazocine was about 7 times more potent an NMA antagonist than (+/-)-pentazocine. The (-)-isomers of both drugs were about 2 times more potent than the (+)-isomers, although the weak NMA antagonist effects of (+)-pentazocine were rather variable. Neither naloxone nor haloperidol affected the NMA antagonist activity of the drugs tested. Examination of the relative NMA antagonist potencies of the compounds suggests that the effect is mediated via an interaction with the phencyclidine receptor. The results are discussed with particular reference to those behavioral effects of cyclazocine and pentazocine which might reflect functional NMA antagonism in vivo.