Summary
Bretylium and tetracaine when perfused at increasing concentrations inhibited and finally blocked discharges elicited by acetylcholine and KCl in adrenergic nerve endings of the isolated perfused heart and less regularly in the isolated perfused spleen of the cat.
There was a direct correlation between the inhibition of the effects of sympathetic nerve stimulation and the inhibition of KCl-induced discharges by bretylium and tetracaine in the heart with regard to both intensity and time course. Acetylcholine-induced release of noradrenaline in the heart was somewhat more resistant to the action of bretylium than acetylcholine-induced antidromic discharges in cardiac adrenergic nerves.
Bretylium and tetracaine inhibited and blocked discharges in sinus nerve afferents elicited by rises in the perfusion pressure and by injection of KCl.
The concentration for complete block in the perfused carotid sinus preparation was 800–1, 000 times higher for bretylium than for tetracaine, whereas bretylium was equally or more potent (depending on the time of interaction) than tetracaine in the isolated perfused heart. Moreover, the effect of bretylium in the heart and spleen developed slowly, increased continuously during the perfusion period and was very resistant to washing out. In contrast, tetracaine achieved its maximum effect on heart, spleen and carotid sinus preparations very rapidly and was readily washed out. The time course and reversibility of the effect of bretylium on baro-receptor afferents were not drastically different from those of tetracaine.
All observations may be explained by the fact that bretylium is a very weak local anaesthetic causing, however, a marked selective local anaesthesia of adrenergic nerve terminals because of its high accumulation in these endings. The adrenergic nerve blocking effect of bretylium seems to be adequately explained by its stabilizing effect on the membrane of the nerve terminals.
Preliminary results of this report have been communicated to the German Pharmacological Society in Mainz at the Spring Meeting 1969 (Haeusler, G., W. Haefely and A. Huerlimann, 1969).
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Haeusler, G., Haefely, W., Huerlimann, A. (1969). On the Mechanism of the Adrenergic Nerve Blocking Action of Bretylium. In: Habermann, E., et al. Naunyn Schmiedebergs Archiv für Pharmakologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-39718-3_326
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