Anticonvulsant action and biochemical effects in DBA/2 mice of CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate), a novel N-methyl-D-aspartate antagonist

Eur J Pharmacol. 1987 Jul 2;139(1):91-6. doi: 10.1016/0014-2999(87)90501-2.

Abstract

CPP has a potent anticonvulsant effect against sound-induced seizures in audiogenic DBA/2 mice. Pretreatment with CPP (0.01-10 nmol i.c.v., 45 min) protects against successive phases of sound-induced seizures in a dose-dependent fashion (ED50, tonic phase, 0.023 nmol; clonic phase, 0.039 nmol; wild running, 0.17 nmol). Systemic administration of CPP (0.001-0.1 mmol/kg i.p., 45 min) produces a similar protection (ED50, tonic phase, 0.0012 mmol/kg; clonic phase, 0.0026 mmol/kg; wild running, 0.021 mmol/kg). Following the administration of a fully anticonvulsant dose of CPP (0.1 mmol/kg i.p., 45 min) to adult DBA/2 mice regional brain glucose (cerebellum and striatum) levels are elevated and lactate (striatum and hippocampus) levels decrease. The CPP-induced changes in alanine, serine and glycine paralleled those of lactate. Aspartate levels are significantly decreased by CPP in the striatum (-21%) and the hippocampus (-23%).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Anticonvulsants / pharmacology*
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / antagonists & inhibitors
  • Brain Chemistry / drug effects*
  • Female
  • Glucose / metabolism
  • Lactates / metabolism
  • Lactic Acid
  • Male
  • Mice
  • Mice, Inbred DBA
  • N-Methylaspartate
  • Piperazines / pharmacology*

Substances

  • Amino Acids
  • Anticonvulsants
  • Lactates
  • Piperazines
  • Aspartic Acid
  • Lactic Acid
  • N-Methylaspartate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Glucose