The selective sigma ligand MS-377 attenuates the blockade by phencyclidine of NMDA-induced intracellular calcium.
The role of MS-377, a novel selective sigma1 ligand currently being developed for the treatment of schizophrenia, in modulating the activities of phencyclidine (PCP) on NMDA-induced calcium increase was examined in primary cultured neocortical neurons using calcium-imaging technique combined with a confocal laser scanning microscope. PCP significantly blocked NMDA-induced increases in intracellular calcium. The blockade by PCP of NMDA response was attenuated by both MS-377 and another highly selective sigma1 ligand, 3-PPP. The results agree with the interpretation that sigma ligands may directly or indirectly modulate NMDA receptor complex functions, and may suggest that MS-377 might be therapeutically useful in cases of PCP-induced psychosis or schizophrenia.
D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D018613:Microscopy, Confocal; D019579:Neocortex / Q000166:cytology / Q000187:drug effects; D010622:Phencyclidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017480:Receptors, sigma / Q000187:drug effects*; D013644:Tartrates / Q000494:pharmacology*
C464615:1-(4-chlorophenyl)-3-(4-(2-methoxyethyl) piperazin-1-yl)methyl-2-pyrrolidinone tartrate; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D010880:Piperidines; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D013644:Tartrates; C026539:preclamol; D010622:Phencyclidine; D002118:Calcium