Darenthin Hypotensive Agent of New Type

Boura, A. L. A.; Green, A.F.; McCoubrey, A.; Laurence, D. R.; Moulton, Rachael S.; Rosenheim, M. L.

doi:10.1016/s0140-6736(59)90465-9

Cited by 50 publications

(32 citation statements)

References 2 publications

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“…Previous experiments (Boura and Green, 1959) have shown that the nictitating membranes of cats injected subcutaneously with 10 mg./kg. bretylium bromide began to relax after 3 hr., were fully relaxed at 12 and 18 hr., and regained their normal tone only after two to three days.…”

Section: Resultsmentioning

confidence: 96%

“…Moreover, the results for various time intervals show that the levels in these tissues are temporally related to the degree of relaxation of the nictitating membrane, a manifestation of the adrenergic neurone blocking action of the drug (Boura and K Green, 1959). Other ganglia and nerve tissues never attained such high concentrations of the drug, and the specificity of the blocking action of bretylium on adrenergic nerves (Boura and Green, 1959) may therefore be related to the preferential accumulation of the drug by the adrenergic neurones. The sympathetic ganglia contained higher concentrations than did their postganglionic trunks, and this may be due to their having a relatively smaller proportion of supporting tissue.…”

Section: Resultsmentioning

confidence: 99%

“…The drug impaired the function of adrenergic neurones in doses which did not affect the parasympathetic or central nervous systems. It has been successfully used to control hypertension in man (Boura, Green, McCoubrey, Laurence, Moulton, and Rosenheim, 1959;Smirk and Hodge, 1959;Dollery, Emslie-Smith and McMichael, 1960). This study of the distribution of the [14C]-labelled drug in cats suggests that the specificity of action of bretylium may be related to its selective accumulation and retention in adrenergic neurones.…”

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confidence: 90%

“…The pharmacology of bretylium (N-o-bromobenzyl-N-ethyl-N,N-dimethyl ammonium) has been described by Boura and Green (1959). The drug impaired the function of adrenergic neurones in doses which did not affect the parasympathetic or central nervous systems.…”

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confidence: 99%

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The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

Boura

Copp

Duncombe

et al. 1960

British Journal of Pharmacology and Chemotherapy

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A study of the distribution of [14C]-labelled bretylium (N-o-bromobenzyl-N ethyl-NN-dimethylammonium) in cat tissues at various times after subcutaneous injection suggests that the specificity of its blocking action on adrenergic neurones may be related to its selective accumulation in these neurones. The rate of rise and fall of concentration in sympathetic ganglia and postganglionic sympathetic nerves showed a close similarity to the time course of the blocking adrenergic neurones as manifested by relaxation of the nictitating membranes. Concentrations found were similar to those in adrenergic nerve trunks when topical application of the drug had caused a local block of conduction. Conduction in other types of nerve could be blocked by topical application, but in general they were less sensitive, heavily myelinated nerves being the most resistant.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 99%

See 2 more Smart Citations

The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

Boura

Copp

Duncombe

et al. 1960

British Journal of Pharmacology and Chemotherapy

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“…This action was studied in greater detail by Exley (1957). Recently bretylium, N-obromobenzyl-N-ethyl-NN-dimethylammonium ptoluene sulphonate, has been introduced by Boura, Green, McCoubrey, Laurence, Moulton, and Rosenheim (1959) as a substance having a similar action which can be used clinically. The action of these two substances on the isolated atria of the rabbit heart has been examined using in some experiments the sympathetically innervated preparation which has been recently described (Hukovid, 1959), and, in some, a doubly innervated preparation so that the vagal fibres or the sympathetic fibres could be stimulated at will.…”

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confidence: 99%

The Action of Sympathetic Blocking Agents on Isolated and Innervated Atria and Vessels

Huković

1960

British Journal of Pharmacology and Chemotherapy

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A preparation is described of isolated rabbit atria with both vagus and sympathetic nerves. The action on it of bretylium and of choline 2,6-xylyl ether bromide (TM10) was studied. A concentration of breylium sufficient to abolish the response to sympathetic stimulation also depressed the response to vagal stimulation. The effect was reversible, though more easily with choline xylyl ether. Both drugs abolished the accelerating action of acetylcholine in the presence of atropine, but they augmented the action of tyramine, and did not reduce that of amphetamine. In the vessels of the perfused rabbit ear they abolished the constrictor effect of nervous stimulation and of acetylcholine, but increased that of tyramine.The substance choline 2,6-xylyl ether (TM10; hereafter called choline xylyl ether) was synthesized by Hey, and Willey discovered that it blocked the response to stimulation of postganglionic adrenergic fibres without affecting the actions of added adrenaline or noradrenaline (Hey and Willey, 1954). This action was studied in greater detail by Exley (1957). Recently bretylium, N-obromobenzyl-N-ethyl-NN-dimethylammonium ptoluene sulphonate, has been introduced by Boura, Green, McCoubrey, Laurence, Moulton, and Rosenheim (1959) as a substance having a similar action which can be used clinically. The action of these two substances on the isolated atria of the rabbit heart has been examined using in some experiments the sympathetically innervated preparation which has been recently described (Hukovid, 1959), and, in some, a doubly innervated preparation so that the vagal fibres or the sympathetic fibres could be stimulated at will. The substances have also been examined for their action on the perfused vessels of the rabbit ear. METHODSTn all experiments on the atria the solution used was: NaCl 9.0 g., KCl 0.42 g., CaCI2 0.24 g., dextrose 2.0 g. and NaHCO3 0.5 g. in 1 litre. The temperature of the bath was 30°. The bath was bubbled with 02. Rabbit's and guinea-pig's atria were set up in the isolated organ bath, as described by Burn (1952 and with the sympathetic nerve were prepared as follows. Rabbits were stunned and killed, and quickly tied out on a table. The skin was removed from the thorax and neck. The vagus nerve and the sympathetic chain of the right side were identified and tied. The trachea and the oesophagus were divided as they entered the thorax. The ventral wall of the chest was removed without disturbing the thymus and neighbouring tissues. The vertebral column was divided with strong scissors between the cervical and thoracic vertebrae. The main vessels were divided in front of the 3rd thoracic vertebra, and the vertebral column was again divided between the 2nd and 3rd thoracic vertebrae. All skeletal muscles were removed and the preparation was immersed in oxygenated solution at 30°. The preparation was left in this solution at least 5 min. The preparation was then cleaned again and fixed on the short part of an L-shaped rod, and then was again immersed in the solution where it remained. Th...

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Bretylium Tosylate as an Antihypertensive Drug

Hurley¹

1960

JAMA

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Darenthin Hypotensive Agent of New Type

Cited by 50 publications

References 2 publications

The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

The Selective Accumulation of Bretylium in Sympathetic Ganglia and Their Postganglionic Nerves

The Action of Sympathetic Blocking Agents on Isolated and Innervated Atria and Vessels

Bretylium Tosylate as an Antihypertensive Drug

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