Pharmacology of postsynaptic alpha-adrenoreceptors in the mouse anococcygeus muscle

1. The alpha-adrenoreceptor agonists noradrenaline (NA), methoxamine, phenylephrine, naphazoline, oxymetazoline, and xylazine produced contractions of the mouse anococcygeus muscle. All were full agonists. 2. Cocaine (2 microM) increased the pD2 values of NA and phenylephrine. 6-hydroxydopamine pretreatment increased the pD2 values of NA, phenylephrine, and xylazine. After both procedures the order of potency of the agonists was oxymetazoline greater than naphazoline greater than NA greater than phenylephrine greater than methoxamine greater than xylazine. 3. The order of potency of antagonists against all six agonists was prazosin greater than phentolamine greater than yohimbine. However, from differences in the pA2 values and slopes of the Schild plots of the antagonists it was possible to distinguish three distinct groups of agonists: the phenylethylamines; the imidazolines; and the thiazine derivative xylazine. 4. The results suggest that the postsynaptic alpha-adrenoreceptor of the mouse anococcygeus muscle may be broadly classified as alpha 1. However, there may be at least three drug recognition sites on the receptor which interact with agonists of differing chemical structure.