THE ACTIONS OF SOME α-ADRENORECEPTOR AGONISTS AND ANTAGONISTS IN AN ANTINOCICEPTIVE TEST IN MICE

1. It has been shown that a number of sympathomimetic drugs, administered subcutaneously, have potent antinociceptive activity in the mouse abdominal constriction test. These drugs were found to be equieffective antagonists of the nociceptive action of acetic acid and acetylcholine. Of the drugs tested, clonidine was the most potent, being almost 60 times more active than morphine, whilst noradrenaline and oxymetazoline were approximately three and five times less active respectively than clonidine. Phenylephrine was without effect after doses of 2 mg/kg. 2. The regression lines relating the magnitude of the antinociceptive effect of noradrenaline and oxymetazoline to log dose were moved to the right in an approximately parallel manner after subcutaneous administration of piperoxane, 8 and 16 mg/kg. The antinociceptive action of clonidine was also antagonised by piperoxane, but to a lesser extent. Phentolamine had no antagonistic effect on any of these three a-agonists after subcutaneous doses of 16 mg/kg. 3. Oxymetazoline and clonidine, when given by intracisternal injection, were approximately eight-three and fifty times more potent respectively than by subcutaneous administration, and their antinociceptive action was not antagonized by piperoxane, 16 mg/kg subcutaneously, or 50 μg/kg intracisternally. 4. It is postulated that the antinociceptive action of the a-agonists is due to an effect on α-adrenoreceptors located on sensory nerve endings in the peritoneum, and that the affinities of these receptors for the α-agonists and antagonists is different from that shown by either pre- or postsynaptic α-adrenoreceptors. It also appears likely that the antinociceptive action of clonidine and oxymetazoline when given by intracisternal injection involves different mechanisms from their peripheral effects.