Anticonvulsant and proconvulsant properties of a series of structural isomers of piperidine dicarboxylic acid.
Anticonvulsant and convulsant effects of various piperidine dicarboxylic acids have been evaluated following their intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection in DBA/2 mice, a strain of mice genetically susceptible to sound-induced seizures. Protection against sound-induced seizures occurred after intraventricular administration of (+/-)cis-2,3-piperidine dicarboxylic acid (0.017-0.045 mumol), (+/-)trans-2,3-piperidine dicarboxylic acid (0.018-0.33 mumol) and (+/-)cis-2,4-piperidine dicarboxylic acid (0.57-1.68 mumol). Protection against sound-induced seizures occurred after intraperitoneal injection of (+/-)cis-2,3-piperidine dicarboxylic acid (0.52-1.8 mmol/kg). Myoclonus or convulsions occurred at various times after the intraventricular injection of cis-2,3-piperidine dicarboxylic acid, trans-2,3-, cis-2,4-, cis-2,5- and cis-2,6-, piperidine dicarboxylic acids, and after the intraperitoneal injection of trans-2,3-piperidine dicarboxylic acid. The latter effect was blocked by pretreatment with 2-amino-7-phosphonoheptanoic acid (0.33 mmol/kg, i.p.) a potent and specific antagonist of excitation induced by N-methyl-D-aspartate. The anticonvulsant action of cis-2,3-piperidine dicarboxylic acid and the convulsant action of trans-2,3-piperidine dicarboxylic acid were associated with predominant antagonist and agonist actions respectively, at receptors preferring N-methyl-D-aspartate.[1]References
- Anticonvulsant and proconvulsant properties of a series of structural isomers of piperidine dicarboxylic acid. Croucher, M.J., Meldrum, B.S., Collins, J.F. Neuropharmacology (1984) [Pubmed]
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