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Inhibition by sigma receptor ligand, MS-377, of N-methyl- D-aspartate-induced currents in dopamine neurons of the rat ventral tegmental area.
Psychopharmacology (Berl). 2002 Apr; 161(1):64-9.P

Abstract

RATIONALE

MS-377 [(R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl) piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate] is a novel anti-psychotic drug candidate with high affinity for sigma receptors but devoid of binding affinity for PCP binding site of NMDA receptor/ion channel complex.

OBJECTIVES

The effects of MS-377 on NMDA receptor and/or its ion channel complex were examined to elucidate the antipsychotic properties of MS-377.

METHODS

We examined the effect of MS-377 on NMDA (N-methyl- D-aspartate)-induced current in acutely dissociated dopamine neurons of rat ventral tegmental area (VTA) using patch clamp whole cell recording.

RESULTS

MS-377 applied in a bath inhibited the peak current evoked by NMDA applied via the U-tube method for 2 s in a concentration-dependent manner. Other sigma receptor ligands, BD-1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), NE-100 (N, N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride) and haloperidol also inhibited NMDA-induced current in a concentration-dependent manner. Interestingly, concomitant application of MS-377 with BD-1063, NE-100 or haloperidol at concentrations that had no effects on NMDA-induced current, potentiated the MS-377-induced inhibition.

CONCLUSIONS

The results suggest that MS-377, as well as other sigma receptor ligands, indirectly acts on the sigma receptor to inhibit glutaminergic transmission mediated by NMDA receptor/ion channel complex in VTA dopamine neurons, thereby inhibiting dopamine release in target VTA areas.

Authors+Show Affiliations

Department of Pharmacology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, 734-8551, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11967632

Citation

Yamazaki, Yuu, et al. "Inhibition By Sigma Receptor Ligand, MS-377, of N-methyl- D-aspartate-induced Currents in Dopamine Neurons of the Rat Ventral Tegmental Area." Psychopharmacology, vol. 161, no. 1, 2002, pp. 64-9.
Yamazaki Y, Ishioka M, Matsubayashi H, et al. Inhibition by sigma receptor ligand, MS-377, of N-methyl- D-aspartate-induced currents in dopamine neurons of the rat ventral tegmental area. Psychopharmacology (Berl). 2002;161(1):64-9.
Yamazaki, Y., Ishioka, M., Matsubayashi, H., Amano, T., & Sasa, M. (2002). Inhibition by sigma receptor ligand, MS-377, of N-methyl- D-aspartate-induced currents in dopamine neurons of the rat ventral tegmental area. Psychopharmacology, 161(1), 64-9.
Yamazaki Y, et al. Inhibition By Sigma Receptor Ligand, MS-377, of N-methyl- D-aspartate-induced Currents in Dopamine Neurons of the Rat Ventral Tegmental Area. Psychopharmacology (Berl). 2002;161(1):64-9. PubMed PMID: 11967632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition by sigma receptor ligand, MS-377, of N-methyl- D-aspartate-induced currents in dopamine neurons of the rat ventral tegmental area. AU - Yamazaki,Yuu, AU - Ishioka,Miwa, AU - Matsubayashi,Hiroaki, AU - Amano,Taku, AU - Sasa,Masashi, Y1 - 2002/02/27/ PY - 2001/09/03/received PY - 2002/01/09/accepted PY - 2002/4/23/pubmed PY - 2002/9/11/medline PY - 2002/4/23/entrez SP - 64 EP - 9 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 161 IS - 1 N2 - RATIONALE: MS-377 [(R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl) piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate] is a novel anti-psychotic drug candidate with high affinity for sigma receptors but devoid of binding affinity for PCP binding site of NMDA receptor/ion channel complex. OBJECTIVES: The effects of MS-377 on NMDA receptor and/or its ion channel complex were examined to elucidate the antipsychotic properties of MS-377. METHODS: We examined the effect of MS-377 on NMDA (N-methyl- D-aspartate)-induced current in acutely dissociated dopamine neurons of rat ventral tegmental area (VTA) using patch clamp whole cell recording. RESULTS: MS-377 applied in a bath inhibited the peak current evoked by NMDA applied via the U-tube method for 2 s in a concentration-dependent manner. Other sigma receptor ligands, BD-1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), NE-100 (N, N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride) and haloperidol also inhibited NMDA-induced current in a concentration-dependent manner. Interestingly, concomitant application of MS-377 with BD-1063, NE-100 or haloperidol at concentrations that had no effects on NMDA-induced current, potentiated the MS-377-induced inhibition. CONCLUSIONS: The results suggest that MS-377, as well as other sigma receptor ligands, indirectly acts on the sigma receptor to inhibit glutaminergic transmission mediated by NMDA receptor/ion channel complex in VTA dopamine neurons, thereby inhibiting dopamine release in target VTA areas. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/11967632/Inhibition_by_sigma_receptor_ligand_MS_377_of_N_methyl__D_aspartate_induced_currents_in_dopamine_neurons_of_the_rat_ventral_tegmental_area_ L2 - https://dx.doi.org/10.1007/s00213-002-1023-4 DB - PRIME DP - Unbound Medicine ER -