cgp-39653 and norbinaltorphimine

The kappa-selective opioid antagonist, norbinaltorphimine (Nor-BNI), was tested against convulsions and mortality induced by the excitatory amino acids, N-methyl-D-aspartic acid (NMDA), (R,S)-alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainic acid and the gamma-aminobutyric acid antagonist, bicuculline. Nor-BNI (10-40 nmol; intracerebroventricularly, i.c.v.) protected against NMDA (0.5-2.0 nmol i.c.v.)-induced convulsions and NMDA (2 nmol i.c.v.) and AMPA (2 nmol i.c.v.)-induced mortality. The opioid antagonist, naloxone (10 nmol i.c.v.), had no protecting activity. In vitro, Nor-BNI competed with the binding of the specific NMDA receptor ligand, [3H]D,L-(E)-2-amino-4-propyl- 5-phosphono-3-pentenoic acid ([3H]CGP 39653, 10 nM; IC50 of 1.63 +/- 0.20 microM) to mouse brain membrane preparations. The results indicate that the protecting activities of Nor-BNI are mediated by NMDA receptor-related mechanisms.

Topics: 2-Amino-5-phosphonovalerate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Bicuculline; Binding, Competitive; Brain; Ibotenic Acid; Injections, Intraventricular; Kainic Acid; Male; Mice; N-Methylaspartate; Naltrexone; Receptors, N-Methyl-D-Aspartate; Seizures