The Influence of Bretylium on the Interactions of Infused Sympathomimetic Amines and Tyramine in the Reserpine‐treated Pithed Rat

Clarke, David E.; Leach, G. D. H.

doi:10.1111/j.1476-5381.1968.tb00981.x

Cited by 17 publications

(14 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may in part be due to the inhibition of monoamine oxidase by bretylium (Malmfors, 1965;Clarke & Leach, 1968;Clarke, 1969;Malmfors & Abrams, 1970), or it may merely reflect mobilization of noradrenaline within the neurone.…”

Section: Discussionmentioning

confidence: 99%

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart

Abbs

Pycock

1973

British J Pharmacology

View full text Add to dashboard Cite

Summary1. The effects of bretylium were investigated on the content and subcellular distribution of noradrenaline in the rat heart and on the response to stimulation of the sympathetic nerves supplying the heart. 2. In most experiments bretylium produced no change in the total noradrenaline content of the heart but significant changes were produced in the subcellular distribution of noradrenaline. 3. Treatment with amphetamine both prevented and antagonized the bretylium-induced adrenergic neurone blockade and most of the accompanying changes in the subcellular distribution of noradrenaline. 4. There was a temporal correlation between the bretylium-induced depletion of noradrenaline from the microsomal (P2) fraction and adrenergic neurone blockade. 5. The onset of adrenergic neurone blockade was also accompanied by an elevation of the noradrenaline content in the low-speed coarse (PWA) fraction and in the mitochondrial (P1.) fraction; this elevation was prevented by pretreatment with a-methyl-p-tyrosine. 6. It is concluded that although the elevation of the noradrenaline content of the P1A and P,B fractions and a depletion of amine from the P2 fraction are associated with the onset of adrenergic neurone blockade only the depletion from the P2 fraction is required for its maintenance. This conclusion supports the hypothesis that only a small portion of the noradrenaline content of an adrenergically-innervated organ is associated with the release of transmitter, for when this small 'store' is depleted, by agents like bretylium, the nerves fail to function.

show abstract

Section: Discussionmentioning

confidence: 99%

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart

Abbs

Pycock

1973

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…It has been postulated that potentiation by bretylium is related to monoamine oxidase inhibition (Goldberg & Sjoerdsma, 1959), which bretylium has been shown to produce (Kuntzman & Jacobson, 1963;Dvornic et al, 1963;Furehgott, 1964;Furchgott & Sanchez-Garcia, 1966;Giachetti & Shore, 1967;Carlsson & Waldeck, 1967). Thus, in reserpinized animals, potentiation of the cardiovascular response to tyramine produced by bretylium might be explained on the basis of this enzyme inhibitory action (Furchgott, 1964;Furchgott & Sanchez-Garcia, 1966;Clarke & Leach, 1968). Goldberg (1964), Sjoqvist (1965, and other workers who have reported interactions between monoamine oxidase inhibitors and sympathomimetic amines, base their explanation on the following sequence of events: when intraneuronal monoamine oxidase is inhibited, the noradrenaline stores increase and hence larger amounts of noradrenaline are liberated by noradrenaline-releasing drugs.…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that bretylium has a monoamine oxidase (MAO) inhibitory action (McCoubrey, 1962;Kuntzman & Jacobson, 1963;Dvornik, Kraml, Dubuc, Tom & Zsoter, 1963;Furchgott, 1964;Furchgott & Sanchez-Garcia, 1966;Giachetti & Shore, 1967;Clarke & Leach, 1968). The effects of typical MAO inhibitors, such as pheniprazine were therefore compared with that of bretylium on the contractor response of aortic strips to potassium (10-40 mM), tyramine (10-6-10`M), nor.…”

Section: Effect Of Pheniprazine Hydrochloridementioning

confidence: 99%

“…Even in isolated atria from the non-reserpinized guinea-pig (Ryall, 1961;Bhagat, 1964), incubation with bretylium, followed by washout, increased the sensitivity to tyramine 4-8 fold, and to noradrenaline, 1-5-2 fold (Wakade, Cervoni & Furchgott, 1964). It was suggested that potentiation by bretylium could be explained on the basis of its monoamine oxidase inhibition (Furchgott, 1964;Furchgott & SanchezGarcia, 1966; Clarke & Leach, 1968). In addition, bretylium and monoamine oxidase inhibitors potentiate the cardiovascular response to tyramine in non-reserpinized animals.…”

Section: Lintroductionmentioning

confidence: 99%

“…The infusion of doses of noradrenaline and its precursors restore the cardiovascular responses of reserpinized animals to tyramine when preceded by injections of bretylium and other monoamine oxidase inhibitors (Clarke & Leach, 1968). In reserpinized guinea-pig atria, pretreatment with bretylium or other monoamine oxidase inhibitors greatly enhanced the aibility of a temporary exposure to noradrenaline to restore the inotropic response to tyramine (Furchgott, 1964).…”

Section: Lintroductionmentioning

confidence: 99%

See 2 more Smart Citations

Bretylium potentiation of the contractor responses of isolated rabbit aortic strips to potassium and tyramine

Kurahashi

Shibata

1971

British J Pharmacology

View full text Add to dashboard Cite

Summary Pretreatment of rabbit aortic strips with bretylium potentiated the contractor response to potassium and tyramine but not to noradrenaline. On the other hand, such pretreatment inhibited the response to nicotine. Even in reserpinized or cold stored aortic strips, pretreatment with bretylium enhanced the contractor response to potassium and tyramine. Pretreatment of fresh, reserpinized, or cold stored aortic strips with pheniprazine potentiated the contractor response to potassium and tyramine. Pretreatment of aortic strips with bretylium or pheniprazine did not potentiate the response to 5‐hydroxytryptamine (5‐HT). The results indicate that both bretylium and pheniprazine potentiate the action of tyramine and potassium, not by presynaptic mechanisms, but by postsynaptic action, causing an increase in the sensitivity of the effector cells to the stimulants.

show abstract

Adrenergic Neuron Blocking Drugs

Maxwell¹,

Wastila²

1977

Antihypertensive Agents

View full text Add to dashboard Cite

The Influence of Bretylium on the Interactions of Infused Sympathomimetic Amines and Tyramine in the Reserpine‐treated Pithed Rat

Cited by 17 publications

References 23 publications

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart

The effects of bretylium on the subcellular distribution of noradrenaline and on adrenergic nerve function in rat heart

Bretylium potentiation of the contractor responses of isolated rabbit aortic strips to potassium and tyramine

Adrenergic Neuron Blocking Drugs

Contact Info

Product

Resources

About