Absence of side-effects in the anticonvulsant action of cortically applied antagonists of N-methyl-D-aspartate.
Three compounds reportedly blocking the N-methyl-D-aspartate (NMDA) receptor, namely 2-amino-5-phosphonovalerate, gamma-D-glutamylglycine and 3-hydroxy-2-quinoxalinecarboxylic acid, were injected subdurally onto the cortex of freely moving rats. All 3 compounds effectively suppressed behavioral and electrographic seizure activity induced by strychnine, morphine and picrotoxin that were administered via the same route. The cortical application of the NMDA-receptor antagonists did not induce behavioral or electrographic changes, and behavioral side-effects commonly observed following intracerebroventricular administration of these compounds were absent. The anatomical separation of anticonvulsant action and side-effects induced by these compounds suggests that this class of compounds may eventually be useful as antiepileptic drugs.
Frenk
H
H
Liban
A
A
Urca
G
G
Teichberg
V I
VI
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D000927:Anticonvulsants; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D004151:Dipeptides / Q000627:therapeutic use*; D009020:Morphine / Q000037:antagonists & inhibitors; D016202:N-Methylaspartate; D010852:Picrotoxin / Q000037:antagonists & inhibitors; D011810:Quinoxalines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013331:Strychnine / Q000037:antagonists & inhibitors; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D015763:2-Amino-5-phosphonovalerate; D000927:Anticonvulsants; D001224:Aspartic Acid; D004151:Dipeptides; D009020:Morphine; D016202:N-Methylaspartate; D010852:Picrotoxin; D011810:Quinoxalines; D013331:Strychnine; D014633:Valine; C045596:3-hydroxy-2-quinoxalinecarboxylic acid; C028929:gamma-glutamylglycine