Quisqualate

Aziridine 269 (Scheme 3.98), on treatment with pyrazole (270) and subsequent TFA deprotection, gave P-pyrazolylalanine 271, first isolated from Citrullus vulgaris (a water melon) and isosteric with histidine [148]. Treatment of 269 with 1,2,4-ox-adiazolidine-3,5-dione 272 gave (S)-quisqualic acid (273), an active ingredient of the ancient Chinese drug Shihchuntze, an anthelmintic made from the seeds of Quisqualis indica [148]. 

Other agonists Quisqualate NMDA AMPA Kainate Kainate... 

PCP is not acting as a competitive inhibitor at the NMDA receptor thus, PCP and NMDA probably do not share a common recognition site. Examination of the effect of PCP on NMDA-induced DA release (figure 1, lower panel) tends to support this conclusion, but is compromised somewhat by the slightly nonparallel shift produced by 2-APV. This may be due to the fact that NMDA may partially activate quisqualate and kainate receptors on those neurons that are not antagonized by 2-APV. 

Huettner, J. E. (1990) Glutamate receptor channels in rat DRG neurons activation by kainate and quisqualate and blockade of desensitization by Con A. Neuron 5, 255-266. 

Mayer, M. L. and Vyklicky, L., Jr. (1989) Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors. Proc. Natl. Acad. Sci. USA 86, 1411-1415. 

Quisqualic acid - has neuroexcitatory activity (stimulant of glutamic acid receptor)... 

Shinozaki, Y. and Ishida, M., Inhibition of quisqualate responses by domoic acid or kainic acid in crayfish opener muscle. Brain Res., 109, 435, 1976. 

Glutamate and Long neurons Quisqualate - depolarizes membranes Seizures... 

The 1,2,4-oxadiazolidinedione ring is part of the natural amino acid L-quisqualic acid. The ring can be constructed by cyclization of ethyl 4-hydroxyallophanate (Scheme 100) <84CC1156,85CC256, 93TA2041). 

X = O, R, R = H) with tetra-(9-acetyl-)S-D-ribofuranose affords 2-(2,3,5-tri-0-acetyl-j6-D-ribofuranosyl)-l,2,4-oxadiazolidine-3,5-dione <81JMC1172). Quisqualic acid is biomimetically synthesized (8-10%) by alkylation of (226) (X = O, R , R = H) with 0-acetylserine in the presence of pyridoxal-5 -phosphate and metal ions <74CPB473,86CPB1473). A synthesis of the neurodepressant quisqualamine has been described (Scheme 102) <828781). 

There are three types of ionotropic glutamate receptors NMDA, a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate receptors (Fig. 1). Each is principally activated by the agonist bearing its name and is permeable to cationic flux hence, their activation results in membrane depolarization. Ionotropic glutamate receptors were originally classified based on three selective, synthetic agonists quisqualate, kainate and NMDA. After the discovery of metabotropic receptors, it became clear that quisqualate also interacts with them. Since that time, quisqualate-sensitive ionotropic receptors have been classified by the more selective agonist AMPA. 

A number of glutamate agonists including NMDA, kainate acid, quisqualic acid, and ibotenic acid, when applied locally, are able to destroy the cholinergic system. 

Metabotropic ACPD, quisqualate MCPG Inhibitory (presynaptic) 1 Ca2+ conductance 1 CAMP Excitatory K+ conductance, t IP3, DAG... 

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