Interactions of Sympathomimetic Drugs and Their Antagonists on the Isolated Atrium

Benfey, B. G.; Greeff, K.

doi:10.1111/j.1476-5381.1961.tb01283.x

Cited by 31 publications

(18 citation statements)

References 8 publications

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“…These evidences support the conclusion that the restarting and recovering effects of acetyl choline originate from some direct effect and not from the endogenously released cate cholamine by acetylcholine. The blocking effects of the adrenolytics on the negative chronotropic and inotropic actions of acetylcholine in the heart were shown by several investigators (11,12) and were confirmed in the present experiments. The order of intensity of the adrenolytics in blocking the negative responses of the atria to acetylcholine accorded well with that of the antagonizing effect of acetylcholine to reverse the atrial depression by the adre nolytics.…”

Section: Differences Of the Effects Of Acetylcholine On The Transupporting

confidence: 77%

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The Antagonizing Mechanism of Acetylcholine on the Atrial Non-Pacemaker Potentials Depressed by Adrenolytics

Misu

Takaori

1964

Japanese Journal of Pharmacology

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Section: Differences Of the Effects Of Acetylcholine On The Transupporting

confidence: 77%

“…(11) have shown that the adreno lytics block parasympathetic effects of the vagus nerve in the isolated guinea-pig's atria.…”

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confidence: 99%

The Antagonizing Mechanism of Acetylcholine on the Atrial Non-Pacemaker Potentials Depressed by Adrenolytics

Misu

Takaori

1964

Japanese Journal of Pharmacology

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“…Being reversible and noncompetitive, this antagonism was unspecific and not due to blockade of adrenaline receptors, although pronethalol inhibited the effect of noradrenaline competitively.It was shown earlier that adrenaline a-receptor blocking drugs antagonize the sympathomimetic actions of butyrylcholine and tyramine on the guinea-pig isolated atrium in concentrations which potentiate the effect of noradrenaline (Benfey & Greeff, 1961). In continuation of 'these studies it was observed that sympathomimetic amines have similar properties, and the mechanism of this effect has been studied.…”

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confidence: 55%

Inhibition of Sympathomimetic Effects on the Heart

Benfey

Varma

1964

British Journal of Pharmacology and Chemotherapy

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The adrenaline /3-receptor blocking drug, pronethalol, and the sympathomimetic amines, (-)-ephedrine, (-)-amphetamine, dexamphetamine, (-)-T -ephedrine and tyramine, inhibited the sympathomimetic effects of butyrylcholine and tyramine on the guinea-pig isolated atrium. Being reversible and noncompetitive, this antagonism was unspecific and not due to blockade of adrenaline receptors, although pronethalol inhibited the effect of noradrenaline competitively.It was shown earlier that adrenaline a-receptor blocking drugs antagonize the sympathomimetic actions of butyrylcholine and tyramine on the guinea-pig isolated atrium in concentrations which potentiate the effect of noradrenaline (Benfey & Greeff, 1961). In continuation of 'these studies it was observed that sympathomimetic amines have similar properties, and the mechanism of this effect has been studied.It was also found that the a-receptor blocking drug, pronethalol, does not inhibit the sympathomimetic actions of butyrylcholine and tyramine by a specific receptor antagonism. METHODSThe guinea-pig atrium was suspended at 30' C in a solution containing (%) NaCl 0.8, NaHCO3 0.1, dextrose 0.1, KCI 0.2, CaCl2 0.2 and NaH2PO4 0.005, which was aerated with 5% carbon dioxide in oxygen. The rate (beats/min) and force of contraction (g) were measured with a Grass force-displacement transducer and recorded either by a Gilson polygraph or by a Twin-Viso Sanborn recorder.In the first part of the experiments the threshold concentration of the antagonists was determined which significantly inhibited the effect of 3 ,ug/ml. of butyrylcholine. The concentration of the antagonists was doubled until the degree of inhibition became significant. Butyrylcholine was first added alone and then with the antagonist and left in the bath until the maximal response was obtained. After 7 min from washing out the organ-bath, butyrylcholine was again added alone to determine if the inhibition was reversible. The concentration of the antagonists which significantly inhibited the effect of butyrylcholine was similarly tested against 0.2 jsg/ml. of noradrenaline and 5 jug/ml. of tyramine.In the second part of the experiments cumulative dose/response curves were determined to characterize the type of the inhibition. Butyrylcholine (1, 3, 10, 30 and 100l4g/ml.), noradrenaline (0.003, 0.03, 0.3, 3 and 30 yg/ml.) and tyramine (0.3, 1, 3, 10 and 30 pg/ml.) were added alone and in the presence of the antagonists. The concentrations remained in the bath until the maximal effect had been observed. To prevent the parasympathomimetic effects of higher concentrations of butyrylcholine (30 and 100 jg/ml.), atropine was added in these experiments in a concentration of 0.7 yg/ml.The guinea-pig isolated atrium is stimulated by butyrylcholine, an effect which is inhibited by ganglion-blocking drugs, is similar to that of acetylcholine in the presence of atropine and is mediated by endogenous catechol amines (Holtz & Westermann, 1955; Holtz, 1959).

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“…It may be worth mentioning that the concentrations of phenoxybenzamine used in this study did not inhibit stimulation of the atrium by histamine or calcium and were approximately 100 times smaller than those needed to potentiate stimulation by noradrenaline (Benfey & Greeff, 1961).…”

Section: Resultsmentioning

confidence: 99%

“…As the adrenaline antagonist, phenoxybenzamine, prevents vagal slowing of the heart of the spinal dog (Benfey, 1962) and converts vagal inhibition of the guineapig isolated atrium into stimulation (Benfey & Greeff, 1961), it appeared of interest to investigate its antagonism of acetylcholine. Cholinergic blockade by the related drug, dibenamine, in the rat isolated atrium, was briefly mentioned by Furchgott (1954).…”

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confidence: 99%

Antagonism of Acetylcholine by Adrenaline Antagonists

Benfey

Grillo

1963

British Journal of Pharmacology and Chemotherapy

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Phenoxybenzamine antagonized the inhibitory action of acetylcholine on the guineapig isolated atrium. The antagonism was slow in onset, very slowly reversible, and could be overcome by increased concentrations of acetylcholine. In contrast, atropine inhibited the action of acetylcholine quickly, and the effect disappeared soon after withdrawal. The pAio of phenoxybenzamine (2 hr of contact) was 6.8, and that of atropine (30 min of contact) was 8.4. In the presence of atropine phenoxybenzamine did not exert a slowly reversible antagonism, and the dose-ratio of acetylcholine returned to normal soon after withdrawal of both drugs. Phenoxybenzamine also antagonized acetylcholine in the guinea-pig isolated ileum, but with higher concentrations acetylcholine did not overcome the antagonism. The pAio (60 min of contact) was 6.6. The pAio of chlorpromazine in the atrium (2 hr of contact) and ileum (60 min of contact) was 5.9. Phentolamine, 2-diethylaminomethylbenzo-1,4-dioxan hydrochloride (883 F), and yohimbine antagonized acetylcholine in the atrium and ileum but required higher concentrations than chlorpromazine.

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Interactions of Sympathomimetic Drugs and Their Antagonists on the Isolated Atrium

Cited by 31 publications

References 8 publications

The Antagonizing Mechanism of Acetylcholine on the Atrial Non-Pacemaker Potentials Depressed by Adrenolytics

The Antagonizing Mechanism of Acetylcholine on the Atrial Non-Pacemaker Potentials Depressed by Adrenolytics

Inhibition of Sympathomimetic Effects on the Heart

Antagonism of Acetylcholine by Adrenaline Antagonists

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