The anticonvulsant potency of (+/-)-2-Amino-7-phosphonoheptanoic acid and (+/-)-2-amino-5-phosphonovaleric acid against metaphit-induced audiogenic seizures in rats.
Male Wistar albino rats were subjected to sound stimulation (100+/-3 dB, 60 s) at hourly intervals after intraperitoneal injection of metaphit (10 mg kg-1). The incidence and severity of audiogenic convulsions increased with time, reached a peak 7-12 h after metaphit administration (ten out of 12 and 2.25+/-0.32), and then gradually decreased until 31 h post-injection when no animal displayed signs of seizure. In order to test anticonvulsant activity on fully developed seizures, antagonists were delivered intracerebroventricularly after the 8th testing. The doses of AP7 were 0.005, 0.01, 0.02, 0.03 and 0.05 micromol, and 0.05, 0.1, 0.2 and 0.3 micromol of AP5, all in 5 microliters of physiological saline. Antagonists inhibited metaphit-induced audiogenic seizures in a dose-related fashion. The minimum doses that completely abolished convulsions were 0.03 and 0.3 micromol for AP7 and AP5, respectively. For suppression of running, clonus and tonus AP7 was 16-18 times more potent than AP5. These results indicate that AP7 is substantially more potent than AP5 against all phases of metaphit-induced audiogenic seizures in rats. (c) 1998 The Italian Pharmacological Society.
Zivanović
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Department of Physiology, School of Medicine, University of Belgrade, Visegradska 26/II, Belgrade, 11000, Yugoslavia.
Susíc
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Stanojlović
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D015763:2-Amino-5-phosphonovalerate; C044705:metaphit; D010622:Phencyclidine; C031231:2-amino-7-phosphonoheptanoic acid