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.
1 Blood pressure, heart rate and evoked cardiovascular reflexes were examined in cats following chronic treatment with haloperidol, at a dose of 1 mg kg-' per day, orally for 23 days. Five days after the final dose the animals were anaesthetized and tested for their reaction to various cardiovascular stimuli and to a number of agonist and antagonist drugs, given both intravenously and into the vertebral artery. 2 It was found that treatment with haloperidol caused hypertension in the cats, as well as a potentiation of the pressor response to bilateral carotid occlusion. The response to 30°head-up tilting was also altered so that in treated cats, the blood pressure returned to normal more rapidly during the tilt. 3 There was no difference in the heart rate of the two groups of cats, nor in the pressor response to intravenous noradrenaline or angiotensin II or to afferent brachial nerve stimulation, nor was the depressor action of bradykinin altered. Hexamethonium reduced the blood pressure in both control and treated cats to approximately the same level. Blood 02, C02, pH and bicarbonate levels were also unaltered by the treatment, as was plasma renin activity. 4 Of the drugs given into the vertebral artery, only noradrenaline, prazosin, ketanserin and haloperidol caused a significantly greater fall in blood pressure in treated than in control cats, while clonidine and St9l were equally effective in both groups. These results suggest that haloperidol treatment has caused a greater modulation of central ml-than of M2-adrenoceptors.
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