Effects of the novel H1 agonists 2-(3-trifluoromethylphenyl)- and 2-(3-bromophenyl)histamine and of 2-(2-thiazolyl)ethylamine on cardiovascular paramenters in the pithed rat

The effect of the newly synthetized H₁ agonists 2-(3-trifluoromethylphenyl)histamine (2-TFMPH) and 2-(3-bromophenyl)histamine (2-BPH) and of the reference compound 2-(2-thiazolyl)ethylamine (2-TEA) on diastolic 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 producinga dimethindene-sensitive, short-lasting vasodepressor response. At the highest dose, 2-TFMPH and 2-BPH produced an additional small vasopressor response, which was followed by a long-lasting vasodepressor effect not counteracted by dimethindene and ranitidine 2-TEA, at the highest dose, induced an additional vasopressor response abolished by prazosin plus rauwolscine. Basal heart rate was increased by 2-TEA (in a desipramine-sensitive manner) but not affected by 2-TFMPH or 2-BPH. In conclusion, 2-TFMPH and 2-BPH are potent H₁ agonists, devoid of an indirect sympathomimetic effect; at high doses, they produce a vasodepressor response not mediated via histamine receptors.Recipient of a fellowship provided by the Alexander von Humboldt-Stiftung (Bonn, Germany)