Antagonism of the Hypotensive Action of Bethanidine and Debrisoquine by Tricyclic Antidepressants

Skinner, C; Coull, D.C.; Johnston, Alan

doi:10.1016/s0140-6736(69)90262-1

Cited by 32 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It enters the neuron via the membrane uptake mechanism; TCA has been shown to antagonize its effect by blocking its uptake (96). It has been well documented that in man the antihypertensive effect of guanethidine-like drugs can be reversed by TCA, leading to loss of effective blood pressure control and /or to progressively greater antihypertensive drug requirements (97). A patient whose pressure was controlled on 75 mg of guanethidine prior to the start of amitriptyline (25 mg t.i.d.)…”

Section: Drug Interactions With Tricyclic Antidepressantsmentioning

confidence: 99%

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

Jefferson

1975

Psychosomatic Medicine

227

View full text Add to dashboard Cite

The tricyclic antidepressants have potent and complex effects on the cardiovascular system, both directly and through interactions with other drugs. Through a combination of anticholinergic activity, direct myocardial depressant activity and an effect on the adrenergic neuron, they can cause a combination of arrhythmias, blood pressure abnormalities and congestive heart failure. These changes, although most common with overdose, can occur at therapeutic levels. In addition a number of drug-drug interactions can occur between the tricyclics and agents used in the treatment of cardiovascular disease, as exemplified by tricyclic antagonism of the antihypertensive effect of guanethidine. Awareness of these factors is necessary to insure proper therapeutic utilization of the tricyclics as well as to treat effectively their toxicity.

show abstract

Section: Drug Interactions With Tricyclic Antidepressantsmentioning

confidence: 99%

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

Jefferson

1975

Psychosomatic Medicine

227

View full text Add to dashboard Cite

show abstract

“…They are thereby taken up and concentrated in ade-quate amounts to dissociate electrical activity in the adrenergic terminals from its customary sequela -norepinephrine release [Boura et al, 1960[Boura et al, , 1962Schanker and M orrison, 1965;Berti and Shore, 1967;M itchell and O ates, 1970]. Potent inhibitors of the amine pump, such as the tri cyclic antidepressants, are known to antagonize the adrenergic neuron blockade evoked by guanethidine, bethanidine and bretylium both in experimental preparations [Stone et al, 1964;Kaumann et al, 1965;C arlsson and Waldeck, 1965], and in man [M itchell et al, 1967;Skinner et al, 1969]. The antagonism is generally attributed to compe tition by the tricyclic compounds for the amine pump receptor and a con sequent reduction of the uptake of the neuron blocking agents.…”

Section: Introductionmentioning

confidence: 99%

Concerning the Role of the Amine Pump of the Adrenergic Innervation of Rabbit Aorta in Sustaining the Neuron Blockade Produced by Bethanidine and Bretylium

Ra¹,

Sb²

1975

J Vasc Res

View full text Add to dashboard Cite

Adrenergic neuron blockade produced in rabbit aortic strips by bretylium and bethanidine has been studied. Differences were noted in the characteristics of approximately equal, strong neuron blockade produced by these two chemically different agents. The blockade produced by bretylium was readily reversed by washout of the drug from the tissue bath whereas blockade produced by bethanidine was slowly reversed. Desmethylimipramine accelerated the recovery after the washout of bretylium, but had little effect in accelerating recovery following the washout of bethanidine. Desmethylimipramine prevented the onset of blockade from bretylium whereas it only delayed the onset of blockade from bethanidine. Desmethylimipramine also completely antagonized an established blockade due to bretylium but only slightly antagonized an established blockade due to bethanidine. It is suggested that the differences observed between these two neuron blocking agents are the result of their differential retention inside the neuron: bretylium is not firmly bound, leaks out of the neuron and goes through a process of recycling across the cell membrane, while bethanidine is more firmly bound inside the neuron than bretylium, only slowly leaks out of the neuron and is not recycled back across the cell membrane.

show abstract

“…It has also been reported to antagonize the antihypertensive action of guanethidine in man by Leishman et al (1963) and Mitchell et al (1967). Skinner et al (1969), Meyer et al (1970), and Fann et al ( 1971 a, b) have noted similar troublesome interactions when tricyclic compounds were administered to patients receiving bethanidine and debrisoquine. Carlsson & Waldeck (1965b) and Mitchell et al (1967), in an attempt to explain the reversal of neurone blockade with antidepressant drugs, were the first to postulate that desmethylimipramine acted by blocking the uptake of guanethidine into adrenergic neurones.…”

Section: Discussionmentioning

confidence: 89%

Guanethidine after twenty years: a pharmacologist's perspective.

Maxwell¹

1982

Brit J Clinical Pharma

View full text Add to dashboard Cite

Antagonism of the Hypotensive Action of Bethanidine and Debrisoquine by Tricyclic Antidepressants

Cited by 32 publications

References 3 publications

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

A Review of the Cardiovascular Effects and Toxicity of Tricyclic Antidepressants

Concerning the Role of the Amine Pump of the Adrenergic Innervation of Rabbit Aorta in Sustaining the Neuron Blockade Produced by Bethanidine and Bretylium

Guanethidine after twenty years: a pharmacologist's perspective.

Contact Info

Product

Resources

About