The distribution of some quaternary ammonium salts in the peripheral nervous system of cats in relation to the adrenergic blocking action of bretylium

摘要

The concentrations of bretylium in the peripheral nervous system of cats after subcutaneous dosage have been compared with those drugs bearing either chemical or pharmacological resemblance to bretylium. o-Bromobenzyltrimethylammonium iodide (383C57), a chemical homologue of bretylium with feeble adrenergic blocking activity, selectively accumulated in adrenergic neurones to attain concentrations comparable with those found for bretylium, but it did not persist in the neurones. {2-(4-Benzoyl-2,6-dimethylphenoxy)ethyl}trimethylammonium, the 4-benzoyl derivative of 2,6-xylyl choline ether (172C58), a pharmacological analogue of bretylium but with little chemical resemblance, had a less marked selective affinity for adrenergic neurones and the concentrations after an effective dose were much lower than found for bretylium. Pentacynium {N1-5-cyano-5,5-diphenylpentyl)-N1N1N2-trimethylethylene-1-ammonium-2-morpholinium di-iodide}, a bis-quaternary ammonium-type ganglion blocking agent, had no selective affinity for adrenergic neurones. Bretylium was not displaced from adrenergic neurones by a subsequent dose of 172C58. The potency and duration of local anaesthetic action of bretylium, 383C57 and 172C58 were roughly parallel to the potency and duration of their adrenergic blocking action. The results are discussed in relation to the role of selective accumulation in adrenergic neurones by bretylium in its adrenergic blocking activity.