Oxymetazoline

Abstract: 1 A modified abdominal constriction test, whereby the drugs used are injected intraperitoneally when the writhing response is maximal, has been used to study the antinociceptive activity of various sympathomimetic drugs. Of those tested, clonidine was the most potent, with an ID50 value in the nanomolar range. (-)-Isoprenaline, (-)-adrenaline and (-)-noradrenaline were only a little less potent. Phenylephrine, the least potent, had only about one-sixtieth of the activity of clonidine. 2 The antinociceptive action appears to occur within the peritoneum, since it was apparent almost immediately after the drugs were injected and was produced by doses far smaller than were effective by the subcutaneous route. 3 α-Adrenoceptors appear to be involved in the reaction, since noradrenaline showed stereospecificity, and the α-adrenoceptor antagonists phentolamine and piperoxan both shifted the dose-response curves of the α-adrenoceptor agonist drugs to the right, usually parallel to the control curves. 4 The high antinociceptive potency of clonidine and oxymetazoline, indicate the importance of α2-adrenoceptors and this was supported by the finding that piperoxan was a more effective antagonist than phentolamine. The moderate potency of phenylephrine suggests that α1-adrenoceptors may also be involved, although the selective α1-antagonist, prazosin, did not antagonize noradrenaline and had antinociceptive activity of its own. 5 β-Adrenoceptors also appear to be involved in the antinociceptive response, since propranalol antagonized the effect of isoprenaline, but not that of clonidine. 6 Piperoxan was a very effective antagonist of morphine, while phentolamine had a weaker action. Naloxone had little action against the α-adrenoceptor agonists. 7 Mice pretreated with clonidine or oxymetazoline but not noradrenaline showed a very great cross-tolerance to morphine. Morphine pretreatment caused marked desensitization of itself, but little cross-tolerance to clonidine or oxymetazoline. 8 It is suggested that sensory nerves in the mouse peritoneum have α2- and β-adrenoceptors on their terminals, and possibly α1-receptors also. It is possible that when activated by the appropriate agonists they depress the generation of pain impulses. There is an interaction between the α-adrenoceptors and opioid receptors in the mouse peritoneum.

Abstract: The affinities of 34 adrenergic antagonists for alpha-2 adrenergic receptors were determined from homogenate radioligand binding studies using [3H]yohimbine and [3H]rauwolscine. It has been suggested that alpha-2 adrenergic receptors can be subdivided into alpha-2A and alpha-2B subtypes. Oxymetazoline is selective for alpha-2A receptors, whereas prazosin is alpha-2B selective. Five different tissues were used, each of which has only one of the two subtypes: human platelet (alpha-2A), HT29 cell line (alpha-2A), human cerebral cortex (alpha-2A), neonatal rat lung (alpha-2B), and NG108-15 cell line (alpha-2B). The drug affinities were highly correlated when alpha-2A tissues were compared with alpha-2A tissues (r = 0.97 to 0.98) or when the two alpha-2B tissues were compared (r = 0.99). By contrast, comparison of an alpha-2A tissue with an alpha-2B tissue resulted in poor correlations (r = 0.77 to -0.87). Three new subtype selective drugs were identified among these drugs on the basis of at least a 10-fold greater affinity for one subtype. All three were selective for the alpha-2B subtype: ARC-239 (100-fold selective), chlorpromazine (18-fold selective), and 7-hydroxychlorpromazine (17-fold selective). These studies, by demonstrating distinct pharmacological profiles for the two alpha-2 adrenergic receptor subtypes in several different tissues, further support the existence and definition of these subtypes. The identification of a cell line for each subtype should be useful in the further study of alpha-2 adrenergic receptor subtypes.