Regulation of blood pressure levels by hexamethonium bromide and mechanical devices.

Probably the first studies of the pharmacology of quaternary ammonium compounds were made by Crum-Brown and Fraser in 1868. Burn and Dale (1915) found that, unlike nicotine, tetraethyl-ammonium chloride blocked autonomic ganglia without noticeable initial stimulation. Barlow and Ing (1948a and b), Paton and Zaimis (1948a and b), and Balaban et al. (1949) studied the properties of some chemical relatives of tetra-ethyl-ammonium in which two quaternary nitrogen groups were separated by a chain of CH2 groups. It was found that decamethonium with ten CH2 groups was curare-form, and pentamethonium and hexamethonium with respectively five and six CH2 groups were predominantly ganglion blocking agents. For example, Paton and Zaimis (1949) showed that intravenous injection of pentamethonium iodide relaxed the cat's nictitating membrane which had been caused to contract by preganglionic stimulation. Pentamethonium iodide also prevented the pulse-slowing action of vagal stimulation. Kay and Smith (1950) showed that hexamethonium iodide lessened the secretory response to insulin-induced hypoglycemia but did not prevent the response of gastric secretion to histamine. All of these results are consistent with the view that pentaand hexamethonium salts act chiefly by blocking autonomic ganglia. Organe et al. (1949), and Arnold and Rosenheim (1949) showed that intravenous or intramuscular injections of pentamethonium produced falls of blood pressure in subjects with normal or raised blood pressure. The effect was similar to that of tetra-ethyl-ammonium chloride bit lasted longer and was accompanied by fewer subjective sensations. These authors also noted postural hypotension, and Arnold and Rosenheim concluded that postural hypotension was likely to limit the value of the substance in treatment and that the most promising application was to peripheral vascular disease. Arnold et al. (1949) showed an increase in the flow through the fingers using a finger plethysmograph. Burt and Graham (1950) confirmed the existence of peripheral dilatation in the legs by skin temperature methods but they found little change in the circulation through the arms. Restall and Smirk (1950) made therapeutic use of the postural hypotension to enhance the blood pressure lowering effect of pentaand hexamethonium in patients with high blood pressure. They reported encouraging results which further observations have confirmed (Smirk, 1950a and b; Smirk and Alstad, 1951). They report that a salt-free diet may enhance the effect of methonium salts, an effect of practical importance. Additional clinical reports have been published by Turner (1950), Saville (1950) and Campbell and Robertson (1950) with varying degrees of benefit. The present paper is concerned with the circulatory effect of hexamethonium bromide (H.M.B.) in man. Many similar experiments have been made with pentamethonium bromide (P.M.B.) and no substantial difference in their effects has been detected.