EFFECTS OF THE NOVEL H1 AGONISTS 2-(3-TRIFLUOROMETHYLPHENYL)-AND 2-(3-BROMOPHENYL)HISTAMINE AND OF 2-(2-THIAZOLYL)ETHYLAMINE ON CARDIOVASCULAR PARAMETERS IN THE PITHED RAT

The effect of the newly synthetized H-1 agonists 2-(3-trifluoromethylp henyl)histamine (2-TFMPH) and 2-(3-bromophenyl)histamine (2-BPH) and o f the reference compound 2-(2-thiazolyl)ethylamine (2-TEA) on diastoli c blood pressure and heart rate was studied in pithed and vagotomized rats. 2-TFMPH and 2-BPH were at least equipotent with 2-TEA in produci ng a dimethindene-sensitive, short-lasting vasodepressor response. At the highest dose, 2-TFMPH and 2-BPH produced an additional small vasop ressor response, which was followed by a long-lasting vasodepressor ef fect not counteracted by dimethindene and ranitidine. 2-TEA, at the hi ghest dose, induced an additional vasopressor response abolished by pr azosin plus rauwolscine. Basal heart rate was increased by 2-TEA (in a desipramine-sensitive manner) but not affected by 2-TFMPH or 2-BPH. I n conclusion, 2-TFMPH and 2-BPH are potent H-1 agonists, devoid of an indirect sympathomimetic effect; at high doses, they produce a vasodep ressor response not mediated via histamine receptors.