Anticonvulsant profile of MDL 27,266: an orally active, broad-spectrum anticonvulsant agent.
The novel anticonvulsant substance MDL 27,266 was tested in a variety of anticonvulsant models to assess its anticonvulsant profile, behavioral toxicity and oral bioavailability. Intraperitoneally (i.p.) administered MDL 27,266 afforded complete protection against sound-induced seizures in DBA/2J and Frings audiogenic-seizure (AGS)-susceptible mice (ED50s: 5.0 and 5.1 mg/kg, respectively). It was also effective following i.p. administration to CF#1 mice against maximal electroshock (MES)-, pentetrazole-, picrotoxin-, quisqualic acid-, and strychnine-induced seizures (ED50s: 24.9, 13.8, 43.3, 8.05, and 60.5 mg/kg, respectively). MDL 27,266, in well tolerated oral doses, prevented the expression of stage 5 behavioral seizures in the corneal-kindled rat and myoclonic seizures in the photosensitive baboon, Papio papio. Chronic administration of MDL 27,266 to AGS-susceptible mice did not markedly affect its anticonvulsant potency or efficacy against sound-induced seizures. These results suggest that MDL 27,266 possesses a broad anticonvulsant profile which most closely approximates that of the broad-spectrum prototype antiepileptic drug valproate.
White
H S
HS
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84108.
Patel
S
S
Meldrum
B S
BS
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010215:Papio; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*
D000927:Anticonvulsants; D014230:Triazoles; C067552:MDL 27266