alpha-substituted quisqualic acid analogs: new metabotropic glutamate receptor group II selective antagonists.
Syntheses of both the alpha-methyl and benzyl analogs of quisqualic acid are described. Testing of these compounds for their activity at excitatory amino acid receptors revealed a striking change in activity in comparison to quisqualic acid. This structural modification results in the loss of quisqualate's potent agonist action at both non-NMDA ionotropic glutamate receptors as well as at group I mGluRs, while allowing these analogs to acquire antagonist properties with relative selectivity for group II metabotropic glutamate receptors.
Kozikowski
A P
AP
Drug Discovery Program, Georgetown University Medical Center, Washington, DC 20007-2197, USA.
Steensma
D
D
Varasi
M
M
Pshenichkin
S
S
Surina
E
E
Wroblewski
J T
JT
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D017136:Ion Transport; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016318:Quisqualic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C116445:benzylquisqualic acid; C116446:methylquisqualic acid; D016318:Quisqualic Acid; D002118:Calcium