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. 1994 Mar;111(3):951–955. doi: 10.1111/j.1476-5381.1994.tb14831.x

Possible NMDA antagonist properties of drugs that affect high pressure neurological syndrome.

M A Shuker 1, F Bowser-Riley 1, S N Davies 1
PMCID: PMC1910069  PMID: 7912632

Abstract

1. Previous studies have suggested that a series of drugs modelled on part of the strychnine molecule interfere with the development of high pressure neurological syndrome (HPNS) and it was presumed that this effect was via an action on inhibitory glycinergic transmission. We have now used the rat hippocampal slice preparation to examine the possibility that some of these drugs might instead have an action at the strychnine-insensitive (SI) glycine binding site associated with the NMDA receptor. 2. D-2-Amino-5-phosphonovalerate (AP5) and 7-chlorokynurenate (7CK) had no significant effect on the height of the population spike recorded from the CA1 region in 1 mM Mg2+ medium, but both blocked the multiple population spikes recorded in Mg(2+)-free medium. The effect of 7CK, but not AP5, was reversed by 200 microM D-serine which is consistent with the known antagonist action of 7CK at the SI-glycine site. 3. A derivative of benzimidazole, which shows the clearest structural similarities to known SI-glycine site antagonists and ameliorates HPNS, mirrored the effects of 7CK although it was considerably less potent. 4. Gramine, which exacerbates HPNS, significantly increased the number of population spikes evoked in Mg(2+)-free medium. 5. Mephenesin, which is the most potent known drug in ameliorating HPNS, had no significant effect on the response recorded in 1 mM Mg2+ and significantly reduced the number of population spikes recorded in Mg(2+)-free medium, but this effect was only partially reversed by the addition of D-serine. 6. The results are consistent with the benzimidazole derivative, but not gramine, being an antagonist at the SI-glycine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Bashir Z. I., Tam B., Collingridge G. L. Activation of the glycine site in the NMDA receptor is necessary for the induction of LTP. Neurosci Lett. 1990 Jan 22;108(3):261–266. doi: 10.1016/0304-3940(90)90651-o. [DOI] [PubMed] [Google Scholar]
  2. Bowser-Riley F., Daniels S., Hill W. A., Smith E. B. An evaluation of the structure-activity relationships of a series of analogues of mephenesin and strychnine on the response to pressure in mice. Br J Pharmacol. 1989 Apr;96(4):789–794. doi: 10.1111/j.1476-5381.1989.tb11885.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bowser-Riley F., Daniels S., Smith E. B. Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2-propandiols in the mouse. Br J Pharmacol. 1988 Aug;94(4):1069–1076. doi: 10.1111/j.1476-5381.1988.tb11624.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carling R. W., Leeson P. D., Moseley A. M., Baker R., Foster A. C., Grimwood S., Kemp J. A., Marshall G. R. 2-Carboxytetrahydroquinolines. Conformational and stereochemical requirements for antagonism of the glycine site on the NMDA receptor. J Med Chem. 1992 May 29;35(11):1942–1953. doi: 10.1021/jm00089a003. [DOI] [PubMed] [Google Scholar]
  5. Coan E. J., Collingridge G. L. Magnesium ions block an N-methyl-D-aspartate receptor-mediated component of synaptic transmission in rat hippocampus. Neurosci Lett. 1985 Jan 7;53(1):21–26. doi: 10.1016/0304-3940(85)90091-6. [DOI] [PubMed] [Google Scholar]
  6. Collingridge G. L., Herron C. E., Lester R. A. Synaptic activation of N-methyl-D-aspartate receptors in the Schaffer collateral-commissural pathway of rat hippocampus. J Physiol. 1988 May;399:283–300. doi: 10.1113/jphysiol.1988.sp017080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collingridge G. L., Kehl S. J., McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol. 1983 Jan;334:33–46. doi: 10.1113/jphysiol.1983.sp014478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fagni L., Zinebi F., Hugon M. Helium pressure potentiates the N-methyl-D-aspartate- and D,L-homocysteate-induced decreases of field potentials in the rat hippocampal slice preparation. Neurosci Lett. 1987 Oct 29;81(3):285–290. doi: 10.1016/0304-3940(87)90397-1. [DOI] [PubMed] [Google Scholar]
  9. Halsey M. J. Effects of high pressure on the central nervous system. Physiol Rev. 1982 Oct;62(4 Pt 1):1341–1377. doi: 10.1152/physrev.1982.62.4.1341. [DOI] [PubMed] [Google Scholar]
  10. Kemp J. A., Leeson P. D. The glycine site of the NMDA receptor--five years on. Trends Pharmacol Sci. 1993 Jan;14(1):20–25. doi: 10.1016/0165-6147(93)90108-v. [DOI] [PubMed] [Google Scholar]
  11. Meldrum B., Wardley-Smit B., Halsey M., Rostain J. C. 2-Amino-phosphonoheptanoic acid protects against the high pressure neurological syndrome. Eur J Pharmacol. 1983 Mar 4;87(4):501–502. doi: 10.1016/0014-2999(83)90094-8. [DOI] [PubMed] [Google Scholar]
  12. Millan M. H., Wardley-Smith B., Halsey M. J., Meldrum B. S. Effect of NMDA and 2-amino-7-phosphonoheptanoate focal injection into the ventrolateral thalamic nucleus on the high pressure neurological syndrome in the rat. Brain Res. 1990 Jan 22;507(2):354–356. doi: 10.1016/0006-8993(90)90298-p. [DOI] [PubMed] [Google Scholar]
  13. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  14. Pralong E., Millar J. D., Lodge D. Specificity and potency of N-methyl-D-aspartate glycine site antagonists and of mephenesin on the rat spinal cord in vitro. Neurosci Lett. 1992 Feb 17;136(1):56–58. doi: 10.1016/0304-3940(92)90646-o. [DOI] [PubMed] [Google Scholar]
  15. Thomson A. M. Glycine is a coagonist at the NMDA receptor/channel complex. Prog Neurobiol. 1990;35(1):53–74. doi: 10.1016/0301-0082(90)90040-n. [DOI] [PubMed] [Google Scholar]
  16. Zinebi F., Fagni L., Hugon M. The influence of helium pressure on the reduction induced in field potentials by various amino acids and on the GABA-mediated inhibition in the CA1 region of hippocampal slices in the rat. Neuropharmacology. 1988 Jan;27(1):57–65. doi: 10.1016/0028-3908(88)90201-8. [DOI] [PubMed] [Google Scholar]

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