A series of novel 1-substituted-4-(3-methylphenyl)-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-ones were synthesized by the cyclization of 2-hydrazino-3-(3-methylphenyl) quinazolin-4(3H)-one with various one carbon donors. The starting material 2-hydrazino-3-(3-methylphenyl)quinazolin-4(3H)-one, was synthesized from 3-methylaniline by a novel innovative route. When tested for their in vivo H₁-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly, whereas the compound 1-methyl-4-(3-methylphenyl)-1,2,4-triazolo[4,3-a]quinazolin-5(4H)-one II was found to be equipotent (percent protection 70.0%) with the reference standard chlorpheniramine maleate (percent protection 71%). Compound II show negligible sedation (7%) when compared to chlorpheniramine maleate (25%). Hence it could serve as prototype molecule for further development as a new class of H₁-antihistamines.