Failure of sigma-receptor ligands to reduce the excitatory actions of N-methyl-DL-aspartate on rat spinal neurons in-vivo.

Haloperidol and (+)-3-PPP, compounds with known affinity for the sigma-receptor, have been examined for their ability to reduce the excitatory actions of N-methyl-DL-aspartate (NMDLA), quisqualate and kainate on rat spinal neurons in-vivo. The actions of (-)-3-PPP were also tested. Haloperidol was injected intravenously whereas the 3-PPP enantiomers were administered by microelectrophoresis. Haloperidol had little effect on excitations evoked by NMDLA, quisqualate or kainate whereas both (+)- and (-)-3-PPP usually enhanced, non-selectively, responses to all three excitatory amino acid analogues. The results support suggestions that phencyclidine (PCP)-like compounds with affinity for both PCP and sigma-receptors reduce neuronal excitations mediated by the N-methyl-D-aspartate (NMDA) receptor via a selective effect at the PCP site.