THE STRUCTURE‐ACTIVITY RELATIONSHIPS OF <i>BETA</i> ADRENERGIC DRUGS AND <i>BETA</i> ADRENERGIC BLOCKING DRUGS

Ariëns, E. J.

doi:10.1111/j.1749-6632.1967.tb41232.x

Cited by 133 publications

(45 citation statements)

References 55 publications

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“…Its bronchodilator effect in vivo has been reported to be similar to that of adrenaline (Engelhardt et al, 1961) and weaker than that of isoprenaline (Shanks et al, 1967). The finding that protokylol is twice as potent as isoprenaline does not agree with Chen (1956) or Ariens (1967). Chen found protokylol and isoprenaline to be equipotent on guinea-pig trachea, whereas Ariens, using stimulated calf tracheal muscle, reported that the high melting point isomer of protokylol was eight times more potent than isoprenaline, whereas the low melting point isomer was equipotent.…”

Section: Discussioncontrasting

confidence: 54%

The Actions of Orciprenaline and Protokylol on Guinea‐pig Trachea

Chahl

O’Donnell

1968

British Journal of Pharmacology and Chemotherapy

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Section: Discussioncontrasting

confidence: 54%

The Actions of Orciprenaline and Protokylol on Guinea‐pig Trachea

Chahl

O’Donnell

1968

British Journal of Pharmacology and Chemotherapy

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“…Blackburn et al (1970) reported that the drug was devoid of 3-adrenoceptor stimulant action. We have found a minor positive chronotropic and inotropic action, which is interesting from the structure-action point of view in that the presence of the phenolic OH in the para position might have been expected to confer some stimulant activity (Ariens, 1967). It has usually been assumed that the /3-adrenoceptors subserving inotropic and chronotropic functions are similar, but there are theoretical considerations which permit the hope that it would be possible to find a drug which could stimulate the one and not the other (Vaughan Williams, 1970a).…”

Section: Inotropic Actionmentioning

confidence: 87%

A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

Singh

Williams

1970

British J Pharmacology

383

127

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Summary Both MJ 1999 and AH 3474 protected guinea‐pigs anaesthetized with urethane against ouabain‐induced ventricular fibrillation. MJ 1999 had 1/90, and AH 3474 1/30, of the activity of procaine in reducing the height of the action potential of frog sciatic nerve. MJ 1999 and AH 3474 reduced the rate of rise of intracellularly recorded action potentials at concentrations in excess of 160 × 10−6m (50 mg/l.). It was concluded that direct depression of depolarization could have contributed little to the protection against ouabain‐induced fibrillation. MJ 1999, but not AH 3474, greatly prolonged the duration of the action potential in acute experiments on isolated atrial and ventricular muscle, and prolonged the Q‐Tc interval of the electrocardiogram in anaesthetized guinea‐pigs. It is suggested that this effect contributes to anti‐arrhythmic activity. At concentrations up to 80 × 10−6m AH 3474 had positive chronotropic and inotropic effects on isolated rabbit atrial muscle, but at higher concentrations these were superseded by negative effects. MJ 1999 was depressant at all concentrations studied, the threshold concentrations being 19 × 10−6m for chronotropic, and 162 × 10−6m for inotropic effects.

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“…It is known that yohimbine blocks adrenaline contractions in rat isolated vas deferens (Martins & Valle, 1939) and that antagonism of piperoxan towards (±)-noradrenaline follows receptor theory (Ariens, 1967). It is apparently contradictory that these antagonists can potentiate the effect of sympathetic stimulation (Ohlin & Stromblad, 1963;Swedin, 1972) and that phentolamine can potentiate the effects of noradrenaline (Barnett, Greenhouse & Taber, 1968), in this preparation.…”

Section: Introduction Methodsmentioning

confidence: 99%

Dual Effect of Α‐adrenoceptor Antagonists in Rat Isolated Vas Deferens

Jurkiewicz

1976

British J Pharmacology

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I In rat isolated vas deferens, the isotonic contractile responses to low doses of noradrenaline or adrenaline were antagonized, and those to high doses were potentiated, by yohimbine, piperoxan, phentolamine and tolazoline. Effects due to intermediate doses were not affected, or were potentiated within about 30 min, following an initial inhibition. 2 The a-adrenoceptor blockers thus caused a shift to the right and an increase of the maximum height of log dose-response curves of a-adrenoceptor stimulants. For a given dose of antagonist, the onset was slower for the potentiating than for the blocking effect. 3 The shift to the right induced by piperoxan and yohimbine on dose-response curves of noradrenaline and adrenaline was analysed with the Schild plot, and the slopes obtained, around 0.3, were lower than expected from receptor theory. When cocaine was used to block neuronal uptake, the slopes were close to 1.0. 4 The increase in maximum response to noradrenaline and adrenaline induced by a-adrenoceptor blockers was dependent on the time of incubation, on the dose of antagonist, and on the initial height of responses to the agonist. A less pronounced potentiation was also obtained when acetylcholine was used as agonist. 5 The findings are explained in terms of receptor theory as being due to a dual effect of aadrenoceptor antagonists; competitive antagonism proper, which may be disclosed after blockade of neuronal uptake, and an interaction at a different locus, which results in potentiation of the effects of noradrenaline and adrenaline.

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THE STRUCTURE‐ACTIVITY RELATIONSHIPS OF BETA ADRENERGIC DRUGS AND BETA ADRENERGIC BLOCKING DRUGS

Cited by 133 publications

References 55 publications

The Actions of Orciprenaline and Protokylol on Guinea‐pig Trachea

The Actions of Orciprenaline and Protokylol on Guinea‐pig Trachea

A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474

Dual Effect of Α‐adrenoceptor Antagonists in Rat Isolated Vas Deferens

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