[Inhibition of metaphit-induced audiogenic seizures by 2-amino-7-phosphonoheptanoic acid].
The anticonvulsant potency of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, 2-amino-7-phosphonoheptanoic acid (APH) was investigated in the model of epilepsy induced by systemic administration of metaphit (1-(1-(3-isothiocyanatophenyl)-cyclohexyl)-piperidine). Male Wistar rats were injected with metaphit intraperitoneally (10 mg/kg, i.p.) and exposed to intense audio stimulation (electric bell generating 100 +/- 3 dB at animal level for 60 s) one hour after administration and at 1-h intervals thereafter. Audiogenic seizures consisted of wild running followed by clonic and tonic convulsions. The incidence and severity of seizures increased with time, reaching a peak 7-12 h after metaphit administration, and then gradually decreased until 31 h, when no animal responded. APH was injected intracerebroventricularly (0.005; 0.01; 0.02; 0.03 and 0.05 micromole i.c.v. in 5 microl of sterile saline) after 8 hours of seizure responses. APH inhibited seizures in a dose-dependent manner. Minimum dose which completely blocked seizures in all animals was 0.03 micromole. After varying periods of time, seizures reappeared. The present results demonstrate that APH acts as anticonvulsant in metaphit's model of audiogenic seizures in rats.
Susić
Veselinka
V
Hivanović
Dragana
D
Stanojlović
Olivera
O
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D000927:Anticonvulsants; D015763:2-Amino-5-phosphonovalerate; C044705:metaphit; D010622:Phencyclidine; C031231:2-amino-7-phosphonoheptanoic acid