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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Geelhand, M. Raes, A. D'hooge, R. De Deyn, P. P. Van Bogaert, P. P. |
| Description | Author Affiliation: D'Hooge R ( Laboratory of Neurochemistry and Behaviour, Born-Bunge Foundation, University of Antwerp, Belgium.) |
| Abstract | 1. CGP 40116 is the active (R)-enantiomer of the most potent N-methyl-D-aspartic acid (NMDA) receptor antagonist presently available: 2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849). In this study, we describe the effect of CGP 40116 on whole-cell currents induced by excitatory amino acids in cultured mouse spinal cord cells by use of the whole-cell patch-clamp technique. 2. We found that application of CGP 40116 in the nM range, concentration-dependently inhibited whole-cell current evoked by 20 microM NMDA in mouse cultured spinal neurones (IC50 +/- s.e. mean 48 +/- 8 nm CGP 40116). 3. The compound appeared to be highly selective for the NMDA current. At concentrations as high 1 microM, currents evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid were not affected by CGP 40116. The threshold concentration for antagonism of NMDA-induced responses was 10 nM suggesting a selectivity ratio of > or = 100 fold for NMDA receptors versus AMPA or kainate receptors. 4. CGP 40116 produced a parallel rightward displacement of the NMDA log concentration-current curve indicating competitive antagonism at the transmitter recognition site of the NMDA receptor complex. An apparent dissociation constant for the antagonist was calculated from the displacement of the agonist concentration-current curve: 117 +/- 53 nM CGP 40116 (estimated Kd +/- s.e.). Like other competitive NMDA antagonists, CGP 40116 blocked NMDA-evoked current in a voltage-independent manner. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 120 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1997-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | 2-Amino-5-phosphonovalerate Analogs & Derivatives Excitatory Amino Acid Antagonists Pharmacology N-Methylaspartate Antagonists & Inhibitors Spinal Cord Drug Effects Animals Cells, Cultured Dose-Response Relationship, Drug Mice Physiology Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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