Further studies on the adrenergic neuron blocking activity of some β-adrenoceptor antagonists and guanethidine

Abstract

The effects of low (0.2) and high (20 μg ml⁻¹) concentrations of (±)- and (+)-propranolol, (±)-, (+)- and (-)-sotalol and guanethidine were tested for their ability to reduce responses to sympathetic stimulation in the isolated vas deferens preparation from the guinea-pig. At 0.2 μf ml⁻¹ all drugs produced a slowly developing reduction in the responses to sympathetic stimulation while responses to noradrenaline were largely unchanged. The blockade, which was similar in extent in all six compounds, was reversed by (+)-amphetamine but not by washing. With high concentrations of and (±)-propranolol and guanethidine, the block was rapid in onset and rate and responses to noradrenaline were potentiated. The block was reversed by washing and unaffected by (+)-***amphetamine. Sotalol and its isomers, which possess little non-specific depressant activity, had qualitatively similar actions at 0.2 and 20 μg ml⁻¹. At the latter concentration responses to noradrenaline were potentiated. The results suggest that low concentrations of the β-adrenoceptor antagonists produce a blockade which is typical of guanethidine-like drugs. At high concentrations non-specific depressant (local anaesthetic) actions of propranolol and its isomers are largely responsible for the blockade. A similar mechanism may also operate when high concentrations of guanethidine are used.