Linked Life Data

3191892

Source:http://linkedlifedata.com/resource/pubmed/id/3191892

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1989-1-3
pubmed:abstractText
LY201116 [4-amino-N-(2,6-dimethylphenyl)benzamide], an effective anticonvulsant in several animal models, is rapidly metabolized by N-acetylation in rats, mice and monkeys. In an attempt to preclude metabolic N-acetylation sterically, we investigated LY201409, an analogue possessing two methyl groups ortho to the 4-amino substituent. This structural modification successfully altered the metabolic pathway, and LY201409 displayed potent anticonvulsant activity. LY201409 antagonized maximal electroshock (MES)-induced seizures with ED50 values of 16.2 and 4.2 mg/kg after oral administration to mice and rats, respectively. The compound did not effectively antagonize seizures induced by a variety of chemical convulsants in rats, but did block pentylenetetrazol-induced seizures in mice. Thus, among the classic anticonvulsants, the profile of phenytoin most closely resembles that of LY201409. Studies conducted with the rotorod and horizontal screen assays in mice and behavioral studies in rats suggested that doses of LY201409 that produced CNS side-effects such as sedation or ataxia were well separated from the anti-MES doses. LY201409 was a potent, dose-dependent potentiator of hexobarbital-induced sleeping time in mice. Oral administration of 6.0 mg/kg led to a 372% increase in sleep time relative to control values. Although LY201409 is a potent and effective anticonvulsant, it is also one of the most potent potentiators of hexobarbital-induced sleep time yet described.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0013-9580
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
760-9
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:articleTitle
Pharmacology of LY201409, a potent benzamide anticonvulsant.
pubmed:affiliation
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
pubmed:publicationType
Journal Article