Anticonvulsant effects of a novel aminobenzamide (LY201116) in mice.
The drug 4-amino-N-(2,6-dimethylphenyl)benzamide(LY201116) is a potent and selective anticonvulsant in the maximal electric shock test in mice. The ED50 values after oral and intravenous administration were 1.7 mg/kg and 0.51 mg/kg, respectively. For comparison, the oral and intravenous ED50 values for the anticonvulsant phenytoin which is selective for the maximal electric shock test were 9.1 and 8.5 mg/kg, respectively. After oral administration, LY201116 had a protective index (ED50 to produce neurological impairment, divided by ED50 on the maximal electric shock) of 13.5. After 4 days of administration, there was no evidence of the development of tolerance to the anticonvulsant effects of LY201116. The hexobarbital-induced sleeping time was not significantly affected by either acute or chronic administration of LY201116 for 4 days. In combination studies with the anticonvulsants phenytoin and carbamazepine which are selective for the maximal electric shock test, LY201116 produced dose-additive effects which suggest that it produces its anticonvulsant action through the same mechanism of action as these prototype anticonvulsants.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
J D
JD
Leander
R R
RR
Lawson
D W
DW
Robertson
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D004597:Electroshock; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology
D000927:Anticonvulsants; D001549:Benzamides; D010672:Phenytoin; C055323:ameltolide; D010634:Phenobarbital