(+/-)-cis-2,3-Piperidine dicarboxylic acid is a partial N-methyl-D-aspartate agonist in the in vitro rat cerebellar cGMP model.
The effect of (+/-)-cis-2,3-piperidine dicarboxylic acid [+/-)-cis-2,3-PDA) on formation of cyclic GMP by immature (7-8 day) rat cerebellar slices has been studied. Using magnesium free medium containing the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX), (+/-)-cis-2,3-PDA behaves as an NMDA partial agonist. Thus in this medium, (+/-)-cis-2,3-PDA stimulates cyclic GMP formation, an effect completely blocked by the potent, specific NMDA antagonist (+/-)-2-amino-7-phosphonoheptanoic acid [+/-)-APH) with a Ki = 17.1 microM. The production of cyclic GMP by the full agonist (+/-)-trans-2,3-PDA, was also blocked by (+/-)-APH, suggesting that in this preparation it activates NMDA receptors. (+/-)-trans-2,3-PDA was approximately half as potent as NMDA. By constructing dose response curves to NMDA in the presence of increasing concentrations of (+/-)-APH or (+/-)-APV, these compounds were shown to be competitive NMDA antagonists using Schild analysis.
Leach
M J
MJ
Marden
C M
CM
Canning
H M
HM
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002531:Cerebellum / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D000596:Amino Acids; D000927:Anticonvulsants; D010875:Pipecolic Acids; D001224:Aspartic Acid; C029262:2,3-piperidinedicarboxylic acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D006152:Cyclic GMP; D014633:Valine; D008274:Magnesium; C031231:2-amino-7-phosphonoheptanoic acid