The antagonism of adrenergic neurone blockade by amphetamine and dexamphetamine in the rat and guinea‐pig

Abstract

1 In isolated rat mesentery preparations, intra-arterial injection of the following drugs rapidly suppressed vasoconstrictor responses to sympathetic nerve stimulation: bretylium (75–100 μg), guanethidine (10–20 μg) and bethanidine (20–30 μg); with phenoxypropylguanidine (15–30 μg) the onset of blockade was slower. The blockade caused by these or higher concentrations was rapidly abolished by intra-arterial injection of amphetamine (100 μg) as also was the blockade caused by infusing bretylium or guanethidine for 10–20 min. Partial blockade was produced by 20 μg of reserpine and this was only slightly and briefly antagonized by amphetamine. 2 In mesentery preparations taken from rats 24 h after subcutaneous injection of bretylium 50 mg/kg, guanethidine 10 mg/kg, phenoxypropylguanidine 10 mg/kg or reserpine 0·1 mg/kg, responses to sympathetic nerve stimulation were greatly impaired. Only in the preparations from the bretylium-treated rats did amphetamine antagonize the blockade. The adrenergic neurone blocking effect of bethanidine 10 mg/kg was evident at 12 h but not at 24 h after injection. 3 In rat mesentery amphetamine did not cause vasoconstriction but briefly potentiated the vasoconstrictor effect of sympathetic nerve stimulation. Responses to noradrenaline were not importantly affected. 4 The contractile responses of the rat inferior eyelid caused by stimulation of the cervical sympathetic nerve was greatly reduced 17–27 h after subcutaneous injection of bretylium 300 mg/kg, bethanidine 30 mg/kg, guanethidine 10 mg/kg or reserpine 0·3 mg/kg. Intravenous dexamphetamine (0·5 mg/kg) powerfully antagonized the effect of bretylium, weakly antagonized the blockade by bethanidine and guanethidine and caused no change in the response of reserpine-treated animals. 5 The vas deferens taken from guinea-pigs 24 h after subcutaneous injection of either bretylium or guanethidine showed greatly impaired responses to hypogastric nerve stimulation. Amphetamine largely restored the contractile response in bretylium-treated rats but caused only weak antagonism in the guanethidine-treated animals.