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Selective block of N-methyl-D-aspartic acid (NMDA)-evoked whole-cell currents in mouse cultured spinal neurones by CGP 40116.
Br J Pharmacol. 1997 Jan; 120(2):211-4.BJ

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.

Authors+Show Affiliations

Laboratory of Neurochemistry and Behaviour, Born-Bunge Foundation, University of Antwerp, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9117111

Citation

D'Hooge, R, et al. "Selective Block of N-methyl-D-aspartic Acid (NMDA)-evoked Whole-cell Currents in Mouse Cultured Spinal Neurones By CGP 40116." British Journal of Pharmacology, vol. 120, no. 2, 1997, pp. 211-4.
D'Hooge R, Raes A, Van Bogaert PP, et al. Selective block of N-methyl-D-aspartic acid (NMDA)-evoked whole-cell currents in mouse cultured spinal neurones by CGP 40116. Br J Pharmacol. 1997;120(2):211-4.
D'Hooge, R., Raes, A., Van Bogaert, P. P., Geelhand, M., & De Deyn, P. P. (1997). Selective block of N-methyl-D-aspartic acid (NMDA)-evoked whole-cell currents in mouse cultured spinal neurones by CGP 40116. British Journal of Pharmacology, 120(2), 211-4.
D'Hooge R, et al. Selective Block of N-methyl-D-aspartic Acid (NMDA)-evoked Whole-cell Currents in Mouse Cultured Spinal Neurones By CGP 40116. Br J Pharmacol. 1997;120(2):211-4. PubMed PMID: 9117111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective block of N-methyl-D-aspartic acid (NMDA)-evoked whole-cell currents in mouse cultured spinal neurones by CGP 40116. AU - D'Hooge,R, AU - Raes,A, AU - Van Bogaert,P P, AU - Geelhand,M, AU - De Deyn,P P, PY - 1997/1/1/pubmed PY - 1997/1/1/medline PY - 1997/1/1/entrez SP - 211 EP - 4 JF - British journal of pharmacology JO - Br J Pharmacol VL - 120 IS - 2 N2 - 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9117111/Selective_block_of_N_methyl_D_aspartic_acid__NMDA__evoked_whole_cell_currents_in_mouse_cultured_spinal_neurones_by_CGP_40116_ L2 - https://doi.org/10.1038/sj.bjp.0700886 DB - PRIME DP - Unbound Medicine ER -