Alpha adrenergic and histaminergic effects of tolazoline-like imidazolines

For eliciting contraction of rabbit aorta, the relative potency of agonists in terms of negative log molar ED50 were: oxymetazoline (8.4) greater than naphazoline (7.95) greater than phenylephrine (7.31) greater than tetrahydrozoline (6.5) greater than tolazoline (5.80). None of the imidazolines, however, 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. As expected, the contraction of rabbit aorta produced by an imidazole histamine was competitively antagonized by the histamine 1 antagonist, chlorpheniramine (K B 7.6 X 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 which were not influenced by reserpine and cocaine treatment, or treatment with a beta adrenoceptor blocker, propranolol. The histamine 2 receptor antagonist, metiamide, however, selectively blocked the cardiac effects. It is concluded that oxymetazoline and naphazoline do not activate histamine 1 or histamine 2 receptors or beta adrenoceptors. Thus, the drugs are highly specific alpha adrenoceptor stimulants. On the other hand, tetrahydrozoline and tolazoline interact with histamine 2 receptors and with alpha adrenoceptors, but not with histamine 1 receptors or with beta adrenoceptors.