The ACTIONS OF SOME Α‐ADRENORECEPTOR AGONISTS AND ANTAGONISTS IN AN ANTINOCICEPTIVE TEST IN MICE

Abstract

S U M M A R Y1. 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 . 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 pglkg intracisternally.4. It is postulated that the antinociceptive action of the a-agonists is due to an effect on a-adrenoreceptors located on sensory nerve endings in the peritoneum, and that the affinities of these receptors for the a-agonists and antagonists is different from that shown by either pre-or postsynaptic a-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.2 mglkg.

The pharmacology of fluparoxan: a selective α2‐adrenoceptor antagonist

“…The prevention of clonidine-and UK-14304-induced hypothermia is therefore most probably attributable to blockade of central a2-adrenoceptors. The antinociceptive activity of clonidine also appears to be a2-adrenoceptor-mediated (Paalzow & Paalzow, 1976;Skingle et al, 1982), but could have been produced both at peripheral and at central sites (Bentley et al, 1977;Spaulding et al, 1979;Reddy et al, 1980). Impairment of rotarod performance appears to reflect the sedative effects of CX2-adrenoceptor agonists and is believed to be a centrallymediated action (Drew et al, 1979).…”

Antinociceptive and anti-inflammatory activity of a novel quipazine derivative (AAL-13): a selective inhibitor of 5-hydroxytryptamine reuptake

“…The antinociceptive effect of AAL-13 was evident in both inflamed and non-inflamed rat paws, while indomethacin was more effective in the inflamed paws and it raised the pain threshold in non-inflamed paws only at the highest dose. This effect of AAL-13 might be attributed to blocking the reuptake of 5-HT and noradrenaline (Alhaider 1987), since a-adrenoceptor and tryptaminergic agonists have been shown to possess antinociceptive activity (Bently et al 1977;Jaffe & Martin 1985).…”

Angiotensin-(1–7) through Mas receptor activation induces peripheral antinociception by interaction with adrenoreceptors

“…They have traditionally been associated with peripheral hyperalgesia [33,34,[44][45][46]49], but previous studies have reported their participation in peripheral antinociceptive events [14,38,41,47,48]. Therefore, we also investigated the roles of the ␣ 1 -and ␤-adrenoceptors in the antinociceptive effects of Ang- (1-7).…”