Beta‐adrenoceptor blocking drugs: the relevance of intrinsic sympathomimetic activity.

Wj, Louis; McNeil, John J

doi:10.1111/j.1365-2125.1982.tb01935.x

Cited by 16 publications

(5 citation statements)

References 22 publications

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“…There is good evidence from many comparative studies (e.g. Louis & McNeil, 1982) that the therapeutic efficacy of all -adrenoceptor blocking drugs used for the treatment of hypertension is similar with respect to the magnitude of the reduction of elevated blood pressure. This is true irrespective of whether the drugs are ,13-selective or not and whether they possess partial agonist activity or not.…”

Section: Introductionmentioning

confidence: 99%

Is the ISA of pindolol beta 2‐adrenoceptor selective?

Aellig¹,

Clark²

1987

Brit J Clinical Pharma

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1 Pindolol is a 3-adrenoceptor blocking drug with ISA (also called partial agonist activity). This means that in addition to blocking the effects of ,-adrenoceptor agonists, it produces some stimulation of 3-adrenoceptors. 2 In vitro studies with pindolol show that its maximum stimulant action is similar to that of isoprenaline in tissues possessing mainly P2-adrenoceptors, but is negligible in tissues possessing mainly f3l-adrenoceptors. This suggests selective stimulation of P2-adrenoceptors. 3 In man the arteriodilator effects observed after intra-arterially infused pindolol at concentrations within the same range as those producing an antihypertensive effect also suggest a stimulant action on vascular 132-adrenoceptors. 4 The fact that pindolol prevents the reduction of resting heart rate and cardiac output observed after drugs lacking ISA at first sight suggests stimulation of cardiac ,Bl-adrenoceptors. However, human atria possess not only 13l-but also ,32-adrenoceptors, stimulation of which would produce the same effect.5 Although all 3-adrenoceptor antagonists lower blood pressure, recent experiments have shown that those agents with combined ,l-adrenoceptor blocking activity and ISA at those receptors are less effective. This observation lends weight to the thesis that pindolol does not stimulate ,l-adrenoceptors since it lowers blood pressure as effectively as drugs lacking ISA.6 The evidence available therefore suggests that although pindolol blocks both Il-and P2-subtypes, it selectively stimulates ,B2-adrenoceptors.

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Section: Introductionmentioning

confidence: 99%

Is the ISA of pindolol beta 2‐adrenoceptor selective?

Aellig¹,

Clark²

1987

Brit J Clinical Pharma

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“…There have frequently been suggestions that partial agonists would be less likely to induce bronchospasm in asthmatic subjects [33,34,56]. Clinical experience indicates that partial agonists, whether nonselective, beta 1 selective or beta 2 selective, may all induce bronchospasm in susceptible subjects.…”

Section: Central and Peripheral Hemodynamicsmentioning

confidence: 96%

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes

Jd¹

1991

Cardiovasc Drug Ther

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Despite the fact that beta blockers were introduced into clinical practice 25 years ago, new beta blockers with differing kinetic and dynamic profiles continue to be developed and marketed. This overview assesses some of the more extensively studied agents from the point of view of proof of utility and the validity of claims for therapeutic advances. The clinical data suggests that despite the expectations of improvements based on kinetic and dynamic consideration, none of the newer agents have been shown unequivocally, either in terms of efficiency or tolerability, to be an advance over the reference agents, the beta 1 antagonists atenolol and metoprolol. This may be either because such improvements will not occur or because of shortcomings in the design and duration of comparative studies. There are trends to suggest that celiprolol has lesser effects on bronchial function and that it has a lesser impact on lipoprotein profiles. Approaches are suggested that might enable clinicians to appraise for themselves the validity of claims for the improved efficiency of new beta blockers.

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“…The side effects reported with prenalterol have included occasional ventricular ectopic beats, sinus tachycardia, chest pain, palpitations, and feelings of tension (15,47,50). In a few patients, an increase in the severity of arrhythmias was observed (49).…”

Section: Side Effectsmentioning

confidence: 99%

Prenalterol

Vickers

1984

Cardiovascular Drug Reviews

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Prenalterol (H133/22) is the hydrochloride salt of the levorotatory (-) isomer of l-(4-hydroxyphenoxy)-3-isopropyl-amino-2-propanol (Fig. 1). The compound has a molecular weight of 261.75 and a melting point of 125" C. It is freely soluble in water. The pKa values are 9.5 (amine) and 10.0 (phenolic).Prenalterol has been characterized as a selective PI-adrenoceptor agonist. Pharmacologic studies have shown that it has positive inotropic as well as chronotropic effects. At lower doses, the positive inotropic effect is associated with a minimal effect on heart rate; at effective inotropic doses, the drug appears to have less tendency to cause arrhythmias than either cardiac glycosides or other sympathomimetic amines. Clinical studies have shown the utility of prenalterol as a padrenoceptor agonist. It is anticipated that prenalterol will be used in the management of patients with congestive heart failure, myocardial ischemia, and coronary artery disease and in postoperative cardiac surgery. ANIMAL PHARMACOLOGY Cardiovascular Effects lnotropic and Chronotropic PropertiesThe pharmacologic activity of several p-adrenoceptor agonists, including prenalterol, was studied in the norepinephrine-depleted anesthetized cat. Prenalterol increased heart rate but did not dilate the hindlimb vasculature. Isoproterenol and terbutaline caused a dose-dependent increase in heart rate as well as a dilation of the hindlimb vasculature. The ratios of the ED5,, for vasodilation to the ED50 for heart rate for isoproterenol, terbutaline, and prenalterol were 0.3, 0.1, and >600, respectively. These values indicate that prenalterol has a high degree of selectivity for cardiac P-adrenoceptors, while isoproterenol and particularly terbutaline have a higher affinity for vascular p-adrenoceptors (13). PRENALTEROLPrenalterol and terbutaline differed in their relative inotropic and chronotropic activities in the cat. The ratios of the ED5& for heart rate to the maximum dpldt for prenalterol and terbutaline were 0.93 and 0.16, respectively. The ED,, ratio for isoproterenol did not differ significantly from that for prenalterol. Thus it was possible to differentiate between P-agonists with primarily a positive chronotropic or inotropic effect. Terbutaline, a @,-selective agonist, at 36 nmoles/kg i.v., increased heart rate to a greater extent than the contractile force; prenalterol, a PIselective agonist, at 9 nmolesikg i.v., had equal positive inotropic and chronotropic effects.It was hypothesized that both PIand P,-adrenoceptors are present in the sinoatrial (SA) node and in the myocardium of the ventricles, but that their relative distribution differed. The ratio of the 6,to the P,-adrenoceptors appeared to be higher in the ventricle than in the SA node. Terbutaline, therefore, a @,-selective agonist, was more effective on the SA node than on the ventricle, and the chronotropic response to terbutaline was more pronounced than the inotropic response. Prenalterol, on the other hand, produces equal chronotropic and inotropic effects because of its hi...

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Beta‐adrenoceptor blocking drugs: the relevance of intrinsic sympathomimetic activity.

Cited by 16 publications

References 22 publications

Is the ISA of pindolol beta 2‐adrenoceptor selective?

Is the ISA of pindolol beta 2‐adrenoceptor selective?

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes

Prenalterol

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