Synthesis and antihistaminic activity of 3H-benzo [4,5] thieno [2,3-d][1,2,3] triazin-4-ones

In the present study the antihistaminic activity of tricyclic benzothieno 1,2,3-triazine derivatives namely CP-3 (3-(phenyl)-5,6,7,8-tetrahydro, 3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one), CP-5 (3-(3-methyl phenyl)-5,6,7,8-tetrahydro, 3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) and CP-8 (3-(4-chloro phenyl)-5,6,7,8-tetrahydro, 3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) were evaluated using in vitro (isolated guinea pig ileum) and in vivo (bronchodilator activity in guinea pigs) models and the sedative potential of the test compounds were evaluated using acto-photometer in mice. In in vitro antihistaminic study, the CP-3, CP-5, CP-8 and chlorpheniramine maleate (CPM) have shown a rightward shift in concentration response curve (CRC) of histamine with a change in EC(50) values of histamine in all the four tissue preparations. The slope obtained in the schild plot indicated that CP-5, CP-8 and CPM were competitive in nature for H(1)-receptors. However, CP-3 has shown non-competitive antagonism. In in vivo antihistaminic study, the CP-3, CP-5, CP-8 and CPM have shown mean increase in exposition time against histamine challenge compared to control group (p < 0.001). All the test drugs (10 mg/kg) and CPM (2 mg/kg) have offered a significant (p < 0.001) protection against preconvulsive dyspnoea (PCD) compared to control. In conclusion, all the test drugs have shown very good antihistaminic activity and the test drugs have very little sedative action compared to CPM. (C) 2011 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.