ALPHA ADRENERGIC AND HISTAMINERGIC EFFECTS OF TOLAZOLINE-LIKE IMIDAZOLINES

Abstract

For eliciting contraction of rabbit aorta, the relative potency of agonists in terms of negative log molar median effective dose (ED50) were: oxymetazoline (8.4) > naphazoline (7.95) > phenylephrine (7.31) > tetrahydrozoline (6.5) > tolazoline (5.80). None of the imidazolines produced maximal effects equal to that of phenylephrine. All agonists were directly acting agents. The interactions between oxymetazoline and phentolamine or tolazoline and phentolamine were competitive with pA2 values of 8.1 and 8.0, respectively. Phentolamine with tetrahydrozoline, naphazoline or phenylephrine produced nearly equal KB values. Thus, all the agonists and .alpha.-adrenoceptor blockers must act at a common site in rabbit aorta. The contraction of rabbit aorta produced by an imidazole histamine was competitively antagonized by the histamine1 antagonist, chlorheniramine (KB 7.6 .times. 10-9 M). The antagonist failed to block the contraction produced by the imidazolines studied. On guinea-pig aorta the relative potency of the agonists varied greatly. On guinea-pig atria tetrahydrozoline and tolazoline produced positive chronotropic effects not influenced by reserpine and cocaine treatment or treatment with a .beta.-adrenoceptor blocker, propranolol. The histamine2 receptor antagonist, metiamide, however, selectively blocked the cardiac effects. Oxymetazoline and naphazoline do not activate histamine1 or histamine2 receptors of .beta.-adrenoceptors. Thus, the drugs are highly specific .alpha.-adrenoceptor stimulants. Tetrahydrozoline and tolazoline interact with histamine2 receptors and with .alpha.-adrenoceptors but not with histamine1 receptors or with .beta.-adrenoceptors.