Evidence for Glutamate Receptor Subtypes from in Vivo Electrophysiology: Studies with HA-966, Quinoxalinediones and Philanthotoxin
In this chapter we will briefly review some of the evidence from electrophysiological studies of mammalian neurones in vivo which relates to the subtypes of glutamate receptors. In particular we will concentrate on recent experiments elucidating the mechanism of action of HA-966 as an N-methyl-D-aspartate (NMDA) antagonist and of a new tricyclic quinoxalinedione (NBQX) and a wasp venom, philanthotoxin, as quisqualate antagonists. These studies were designed to test the hypothesis that the NMDA subtype and one other non-NMDA subtype of glutamate receptor mediate the excitation of rat spinal and brainstem neurones produced by acidic amino acids.
KeywordsExcitatory Amino Acid Excitatory Amino Acid Receptor Mammalian Neurone Brainstem Neurone Wasp Venom
Unable to display preview. Download preview PDF.
- Aram. J.A., Martin, D., Tomcczyk, M., Zeman, S., Millar, J., Pohler, G. and Lodge, D. Neocortical epileptogenesis in vitro: studies with N-methyl-D-aspartate, phencyclidine, sigma and dextromethorphan receptor ligands. J Pharm Exp Ther 1989; 248: 320–328.Google Scholar
- Davies, J. and Watkins, J.C. Is 1-hydroxy-3-amino-pyrrolidone-2 (HA966) a selective excitatory amino acid antagonist? Nature New Biol 1972; 328: 61–63.Google Scholar
- Honore, T., Davies, S.N., Drejer, J., Fletcher, E.J., Jacobsen, Lodge, D. and Nielsen, F. E. Quinoxalinediones: Potent competitive non-NMDA glutamate receptor antagonists. Science 1988; 241: 701–703.Google Scholar
- Kessler, M., Baudry, M., Terramani, T. and Lynch, G. Complex interactions between a glycine binding site and NMDA receptors. Soc Neurosci Abstr 1987; 13: 760.Google Scholar
- Lodge, D. Aram, J.A., Church, J., Davies, S.N., Martin, D., Millar, J. and Zeman, S. Sigma opiates and excitatory amino acids. In: Excitatory Amino Acids in Health and Disease. Ed. D. Lodge. John Wiley, London. 1988; pp. 237–259.Google Scholar
- Lodge, D. and Johnson, K.M. Non-competitive excitatory amino acid antagonists. Trends Pharm Sci 1990; in press.Google Scholar
- Mayer,2+., Westbrook, G.L. and Guthrie, P.B. Voltage-dependent block by Mg of NMDA responses in spinal cord neurones. Nature 1984; 309: 261–263.Google Scholar
- Ornstein, P.L., Schoeppe, D.D., Leander, J.D., Wong, D.T., Lodge, D. and Mason, N.R. In vitro and in vivo characterization of LY233O53: a structurally novel competitive antagonist. Soc Neurosci Abstr 1989; in press.Google Scholar
- Simmonds, M.A. and Horne, A.L. Antagonism of excitatory amino acids by barbiturates. In: Excitatory Amino Acids in Health and Disease, Ed. D. Lodge. John Wiley, London. 1988; pp. 219–237.Google Scholar
- Watkins, J.C. and Collingridge, G.L. (Eds) The NMDA Receptor. Oxford Univ Press. 1989; in press.Google Scholar
- Watkins, J.C., Krogsgaard-Larsen, P. and Honore, T. Structure-activity relations in the development of excitatory amino acid receptor antagonists. Trends Pharm Sci 1990; in press.Google Scholar
- Watkins, J.C. and Olverman, H. Structural requirements for activation and blockade of EAA receptors. In: Excitatory Amino Acids in Health and Disease, Ed. D. Lodge. John Wiley, London. 1988; pp. 13–45.Google Scholar