Effect of low-affinity NMDA receptor antagonists on electrical activity in mouse cortical slices.
The objective of this study was to investigate the effects of three low-affinity NMDA receptor antagonists, MRZ 2/279 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane HCl), AR-R 15896AR ([+]-alpha-phenyl-2-pyridine-ethanamine diHCl) and dextromethorphan on epileptiform activity in vitro. Epileptiform discharges were elicited in DBA/2 mouse cortical slices by perfusion with Mg(2+)-free artificial cerebrospinal fluid. MRZ 2/279, AR-R 15896AR and dextromethorphan all reversibly decreased the frequency of the discharges in a concentration-dependent manner. The IC(50)'s for MRZ 2/279, AR-R 15896AR and dextromethorphan were 5.2, 10.8 and 55.9 microM, respectively. These low-affinity NMDA receptor antagonists may be proved to be clinically effective with fewer adverse effects than drugs with high-affinity for the NMDA receptor-operated channel.
Naish
Hywel J
HJ
Department of Pharmacology, Therapeutics and Toxicology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Marsh
Wendy L
WL
Davies
John A
JA
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003517:Cyclopentanes / Q000494:pharmacology*; D003915:Dextromethorphan / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011725:Pyridines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology
D003517:Cyclopentanes; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; C096406:alpha-phenyl-2-pyridineethanamine dihydrochloride; D003915:Dextromethorphan; C114144:neramexane