The Effects of Bethanidine on the Peripheral Circulation in Man

Abstract

Bethanidine has been administered intra-arterially and intravenously into normotensive subjects and its effects on the limb blood vessels, arterial blood pressure, vascular sensitivity to noradrenaline and the degree and time course of sympathetic nerve blockade have been studied. The drug caused an initial constriction of hand and forearm vessels which is attributed to release of catechol amines since it is abolished by the prior administration of phenoxybenzamine. The constriction was followed by a sustained vasodilatation lasting between 5 and 20 hr. Sympathetic blockade of hand vessels commenced immediately on infusion and was complete within 1 hr of administration. Recovery occurred in about 5 hr. Sensitivity to intra-arterial noradrenaline was increased within 10 to 15 min of infusion and before sympathetic blockade was complete. Intravenous administration caused a slight rise in blood pressure of supine subjects. Baroreceptor reflex responses of heart and of limb vessels elicited by tilting the subject feet downwards were abolished by bethanidine and postural hypotension occurred. Bethanidine is a potent sympathetic blocking agent in man with properties intermediate between those of bretylium and guanethidine.

Adrenergic Neurone Blocking Agents: Tolerance and Hypersensitivity to Adrenaline and Noradrenaline

“…Nictitating membrane and pressor responses produced by intravenous injections of adrenaline and noradrenaline into cats increased in magnitude after administration of bethanidine, in a similar manner to the increases found after bretylium or guanethidine (Green, 1960;Boura & Green, 1962). In particular, the sensitivity of the nictitating membranes increased with the duration of drug administration to a maximum sensitivity after fully blocking amounts had been given for 14 days, an increase similar to that produced after postganglionic nerve section.…”

“…In this connection Laurence & Nagle (1963) found that in man single doses of bretylium and guanethidine increased the pressor response to intravenous noradrenaline without increasing vasoconstrictor responses in the forearm produced by intra-arterial injection. However, Fewings et al (1964) report an increased sensitivity to intra-arterial noradrenaline after intra-arterial infusion of bethanidine in hand blood flow experiments.…”

Adrenergic Neuron Blocking Drugs

“…Clinical trials with bethanidine have shown that the hemodynamic effects in hypertensive patients are similar to those produced by guanethidine treatment (MONTUSCHI and PICKENS, 1962;JOHNSON et al, 1962;SMIRK, 1963;FEWINGS et al, 1964;BATH et al, 1967). PRICHARD et al (1968) did not show any significant difference between bethanidine and guanethidine in their ability to lower and control blood pressure in hypertensive patients.…”

Observation of changes in volume of a congested limb as a means of studying the behaviour of capacity vessels

“…In normal subjects the reduction in blood pressure was smaller even with suction on parts below the xiphisternum of -50 to -70 mm Hg . In these subjects regional adrenergic block of the sympathetic nerve fibres of a limb segment was obtained by an intra-arterial infusion of bethanidine sulphate (Fewings, Hodge, Scroop & Whelan, 1964) or by local intravenous administration of the drug while the circulation to the limb was occluded (Ardill, Bhatnagar & Fentem, 1967 (Sharpey-Schafer, 1963). 6.…”