The actions of reserpine, guanethidine and metaraminol on cardiac catecholamine stores

Nash, Charles W.; Costa, E.; Brodie, Bernard B.

doi:10.1016/0024-3205(64)90204-8

Cited by 29 publications

(6 citation statements)

References 9 publications

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“…A crucial test of this hypothesis was the demonstration that labelled noradrenaline released by guanethidine appears in the bloodstream unchanged (Nash, Costa & Brodie, 1964). Moreover, in accord with the hypothesis, previous treatment of rats with bretylium antagonizes the depletion of noradrenaline by guanethidine .…”

Section: Discussionmentioning

confidence: 70%

On the Mechanism of Action of Guanethidine and Bretylium

Brodie

Chang

Costa

1965

British Journal of Pharmacology and Chemotherapy

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Guanethidine is often thought to act like bretylium and produce sympathetic blockade by interfering with the process by which nerve impulses invade sympathetic nerve terminals (Boura & Green, 1959;Cass & Spriggs, 1961). Guanethidine, in contrast to bretylium, impairs the capacity of tissues to store noradrenaline (Sheppard & Zimmerman, 1959;Cass, Kuntzman & Brodie, 1960), but this action of the drug is usually dismissed as distinct from its bretylium-like action since the degree of blockade does not parallel the loss of peripheral noradrenaline (Zaimis, 1964). Thus, guanethidine produces complete block of adrenergic transmission before it produces a measurable loss of noradrenaline stores, and the blockade disappears before the amine content is noticeably repleted (Cass & Spriggs, 1961;Sanan & Vogt, 1962). Additional evidence for the view that guanethidine and bretylium act by similar mechanisms is provided by recent studies which show that the sympatholytic effects of both drugs are inhibited by amphetamine-like drugs (Laurence & Rosenheim, 1960;Wilson & Long, 1960;Matsumoto & Horita, 1962).Since bretylium and guanethidine are often used as research tools in studies of adrenergic function, it is important to know whether they do, in fact, act by the same mechanism.Research carried out in this laboratory Schanker & Morrison, 1964;Chang, Costa & Brodie, 1965) indicates that guanethidine is retained in tissues by two processes. One process localizes the drug nonspecifically and is not affected by amphetamine or reserpine; the other involves a specific affinity of the drug for noradrenaline storage compartments and is suppressed by amphetamine or reserpine. The specific process is saturable and takes up three molecules of drug for each molecule of endogenous noradrenaline.Considerable evidence suggests that the adrenergic blockade is related to the amount of guanethidine that accumulates in sympathetic neurones and that the drug in sympathetic nerve endings elicits a persistent depolarization of presynaptic terminals. According to this view, depolarization would increase the permeability of terminal membranes and cause the loss of noradrenaline. The degree of blockade would not be directly related to the noradrenaline level but to the degree of depolarization that causes the amine loss.

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Section: Discussionmentioning

confidence: 70%

On the Mechanism of Action of Guanethidine and Bretylium

Brodie

Chang

Costa

1965

British Journal of Pharmacology and Chemotherapy

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“…distilled water. The effluent contained the acidic deaminated metabolites, 3:4-dihydroxymandelic acid and 3-methoxy-4-hydroxymandelic acid (Nash, Costa & Brodie, 1964). The columns were eluted with 10-15 ml.…”

Section: Cations and Noradrenaline 87 Methodsmentioning

confidence: 99%

The action of extracellular cations on the release of the sympathetic transmitter from peripheral nerves

Boullin¹

1967

The Journal of Physiology

120

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“…This has been previously shown for guanethidine by Kadzielawa (1962) and Abercrombie & Davies (1963). Guanethidine-induced release of labelled noradrenaline from perfused rat hearts has been demonstrated directly by Nash, Costa & Brodie (1964). Despite the similarity between the noradrenaline-depleting actions of guanethidine and (-)-ft-hydroxyphenethylguanidine, these two drugs have markedly different effects on sympathetic transmission.…”

Section: Effects Of Guanethidine and (-)-(3-hydroxyphenethylguanidinementioning

confidence: 55%

A COMPARATIVE STUDY OF THE NORADRENALINE‐DEPLETING AND SYMPATHETICBLOCKING ACTIONS OF GUANETHIDINE AND (—)‐β‐HYDROXYPHENETHYLGUANIDINE

Fielden¹,

Green²

1967

British Journal of Pharmacology and Chemotherapy

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(-)-,f-Hydroxyphenethylguanidine is the most active of a series of aralkylguanidines studied for their ability to lower the noradrenaline content of sympathetically-innervated tissues. It is several times more potent in this respect than guanethidine, but, unlike guanethidine, it produces only weak impairment of sympathetic transmission. In this paper we have compared the mechanisms of noradrenaline depletion by guanethidine and (-)-,8-hydroxyphenethylguanidine, and studied the relationship between noradrenaline depletion and sympathetic blockade. The nature of the adrenergic neurone blocking action of guanethidine is discussed in the light of these results. METHODS

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The actions of reserpine, guanethidine and metaraminol on cardiac catecholamine stores

Cited by 29 publications

References 9 publications

On the Mechanism of Action of Guanethidine and Bretylium

On the Mechanism of Action of Guanethidine and Bretylium

The action of extracellular cations on the release of the sympathetic transmitter from peripheral nerves

A COMPARATIVE STUDY OF THE NORADRENALINE‐DEPLETING AND SYMPATHETICBLOCKING ACTIONS OF GUANETHIDINE AND (—)‐β‐HYDROXYPHENETHYLGUANIDINE

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