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MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells.
Life Sci. 2002 Feb 22; 70(14):1631-42.LS

Abstract

MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate) is a antipsychotic agent that binds to sigma-1 receptor. MS-377 showed anti-dopaminergic and anti-serotonergic activities and antagonistic action against phencyclidine (PCP)-induced behaviors in an animal model. These anti-psychotic activities of MS-377 are attributable to association with sigma-1 receptor. However, the mechanism by which the sigma-1 receptor ligands exact those numerous effects remains to be elucidated. In the present study, we evaluated the effect of MS-377 on N-methyl-D-aspartate (NMDA) receptor ion-channel complex in primary cultured rat neuronal cells. First, we examined the effect of MS-377 on NMDA-induced Ca2+ influx with fura-2/ AM loaded cells. MS-377 showed no effects on the basal Ca2+ concentration and NMDA-induced Ca2+ influx by itself PCP and SKF-10047 reduced the NMDA-induced increase in intracellular Ca2+ concentration. Pre-incubation of 1 microM MS-377 was found to significantly block the reduction by PCP or SKF-10047 of the NMDA-induced Ca2+ influx. Second, the effect of MS-377 on [3H]MK-801 intact cell binding was examined. PCP, haloperidol and (+)-pentazocine inhibited [3H]MK-801 binding, although MS-377 showed no effect by itself Pre-treatment of MS-377 markedly reversed the inhibition of [3H]MK-801 binding by PCP in a dose-dependent manner. These effects of MS-377 may depend on its affinity for the sigma-1 receptor, because MS-377 is a selective sigma-1 receptor ligand without any affinity for NMDA receptor ion-channel complex. These observations suggest that the MS-377 indirectly modulated the NMDA receptor ion-channel complex, and the anti-psychotic activities of MS-377, in part, are attributable to such on action via sigma-1 receptor.

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Publisher Full Text

Authors+Show Affiliations

Karasawa J
Drug Discoverv Institute, Nihon Schering, Inc, Mobara-shi, Chiba, Japan. jkarasawa@schering.co.jp
Yamamoto H
No affiliation info available
Yamamoto T
No affiliation info available
Sagi N
No affiliation info available
Horikomi K
No affiliation info available
Sora I
No affiliation info available

MeSH

AnimalsAntipsychotic AgentsCalciumCells, CulturedDizocilpine MaleateFemaleIon ChannelsNeuronsPhenazocinePhencyclidinePiperazinesPregnancyPyrrolidinesRatsRats, WistarReceptors, N-Methyl-D-AspartateReceptors, sigmaTartratesTritium

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11991251

Citation

Karasawa, Jun-ichi, et al. "MS-377, a Selective Sigma Receptor Ligand, Indirectly Blocks the Action of PCP in the N-methyl-D-aspartate Receptor Ion-channel Complex in Primary Cultured Rat Neuronal Cells." Life Sciences, vol. 70, no. 14, 2002, pp. 1631-42.
Karasawa J, Yamamoto H, Yamamoto T, et al. MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells. Life Sci. 2002;70(14):1631-42.
Karasawa, J., Yamamoto, H., Yamamoto, T., Sagi, N., Horikomi, K., & Sora, I. (2002). MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells. Life Sciences, 70(14), 1631-42.
Karasawa J, et al. MS-377, a Selective Sigma Receptor Ligand, Indirectly Blocks the Action of PCP in the N-methyl-D-aspartate Receptor Ion-channel Complex in Primary Cultured Rat Neuronal Cells. Life Sci. 2002 Feb 22;70(14):1631-42. PubMed PMID: 11991251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells. AU - Karasawa,Jun-ichi, AU - Yamamoto,Hideko, AU - Yamamoto,Toshifumi, AU - Sagi,Naoki, AU - Horikomi,Kazutoshi, AU - Sora,Ichiro, PY - 2002/5/7/pubmed PY - 2002/5/23/medline PY - 2002/5/7/entrez SP - 1631 EP - 42 JF - Life sciences JO - Life Sci VL - 70 IS - 14 N2 - MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate) is a antipsychotic agent that binds to sigma-1 receptor. MS-377 showed anti-dopaminergic and anti-serotonergic activities and antagonistic action against phencyclidine (PCP)-induced behaviors in an animal model. These anti-psychotic activities of MS-377 are attributable to association with sigma-1 receptor. However, the mechanism by which the sigma-1 receptor ligands exact those numerous effects remains to be elucidated. In the present study, we evaluated the effect of MS-377 on N-methyl-D-aspartate (NMDA) receptor ion-channel complex in primary cultured rat neuronal cells. First, we examined the effect of MS-377 on NMDA-induced Ca2+ influx with fura-2/ AM loaded cells. MS-377 showed no effects on the basal Ca2+ concentration and NMDA-induced Ca2+ influx by itself PCP and SKF-10047 reduced the NMDA-induced increase in intracellular Ca2+ concentration. Pre-incubation of 1 microM MS-377 was found to significantly block the reduction by PCP or SKF-10047 of the NMDA-induced Ca2+ influx. Second, the effect of MS-377 on [3H]MK-801 intact cell binding was examined. PCP, haloperidol and (+)-pentazocine inhibited [3H]MK-801 binding, although MS-377 showed no effect by itself Pre-treatment of MS-377 markedly reversed the inhibition of [3H]MK-801 binding by PCP in a dose-dependent manner. These effects of MS-377 may depend on its affinity for the sigma-1 receptor, because MS-377 is a selective sigma-1 receptor ligand without any affinity for NMDA receptor ion-channel complex. These observations suggest that the MS-377 indirectly modulated the NMDA receptor ion-channel complex, and the anti-psychotic activities of MS-377, in part, are attributable to such on action via sigma-1 receptor. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/11991251/MS_377_a_selective_sigma_receptor_ligand_indirectly_blocks_the_action_of_PCP_in_the_N_methyl_D_aspartate_receptor_ion_channel_complex_in_primary_cultured_rat_neuronal_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(01)01549-1 DB - PRIME DP - Unbound Medicine ER -