Linked Life Data

8035421

Source:http://linkedlifedata.com/resource/pubmed/id/8035421

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1994-8-18
pubmed:abstractText
Several 3-substituted pyridazines and a series of imidazo- and triazolopyridazines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures in mice. The most active derivatives, 3-ureidopyridazine 7 and triazolopyridazines 16, 18, 21, and 25 with oral ED50's that ranged from 6.2 to 22.0 mg/kg, were more extensively investigated by evaluating their ability to prevent chemically induced seizures and were compared with phenytoin, phenobarbital, sodium valproate, carbamazepine, and diazepam. 3-amino-7-(2,6-dichlorobenzyl)-6-methyltriazolo-[4,3-b]pyridazine (25) was also protective in the pentylenetetrazole-induced seizures test (ED50 = 76 mg/kg per os) and blocked strychnine-induced tonic extensor seizures (ED50 = 34.5 mg/kg per os). Furthermore, derivative 25 showed anticonvulsant effects on bicuculline- and yohimbine-induced seizures tests in mice. All these results suggest that the pharmacological activity of 25 is partly due to modifications of glycinergic and GABAergic transmission. Moreover, molecular modeling studies based on the antiepileptic drug lamotrigine and the most stable conformer of 25 show structural similarities between these two molecules. This conformer also agrees with the electronic tolerances and volume of benzodiazepine pharmacophore models.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2153-60
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Synthesis and anticonvulsant properties of new benzylpyridazine derivatives.
pubmed:affiliation
Laboratoire de Chimie Thérapeutique and Laboratoire de Pharmacologie et de Pharmacie Clinique, Faculté de Pharmacie, Clermont-Ferrand, France.
pubmed:publicationType
Journal Article