(+/-)-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.