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.
Church
J
J
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Lodge
D
D
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008024:Ligands; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D013116:Spinal Cord / Q000166:cytology; D013237:Stereoisomerism
D008024:Ligands; D010069:Oxadiazoles; D010880:Piperidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; C026539:preclamol; D006220:Haloperidol; D007608:Kainic Acid