Inhibition by sigma receptor ligand, MS-377, of N -methyl- D -aspartate-induced currents in dopamine neurons of the rat ventral tegmental area
| Autor: | Taku Amano, Hiroaki Matsubayashi, Miwa Ishioka, Yuu Yamazaki, Masashi Sasa |
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| Rok vydání: | 2002 |
| Předmět: |
Agonist
medicine.medical_specialty N-Methylaspartate Pyrrolidines medicine.drug_class Sigma receptor Biology Receptors N-Methyl-D-Aspartate Ion channel complex Dopamine Internal medicine medicine Animals Receptors sigma Patch clamp Phosphorylation Rats Wistar Tartrates Pharmacology Dose-Response Relationship Drug Ventral Tegmental Area Ligand (biochemistry) Rats Ventral tegmental area medicine.anatomical_structure Endocrinology nervous system Biophysics NMDA receptor Antipsychotic Agents medicine.drug |
| Zdroj: | Psychopharmacology. 161:64-69 |
| ISSN: | 1432-2072 0033-3158 |
| Popis: | Rationale: MS-377 [(R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl) piperazin-1-yl]methyl-2-pyrrolidinone L-tartate] 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. |
| Databáze: | OpenAIRE |
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