Differentiation of beta 1- and beta 2-adrenoceptor-mediated effects in humans

Brodde, O.‐E.; Daul, A; Wellstein, Anton; Palm, D.; Michel, Miriam; Beckeringh, J. J.

doi:10.1152/ajpheart.1988.254.2.h199

Cited by 28 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Procaterol increases plasma noradrenaline levels while leaving adrenaline concentration unchanged. This differential action suggests a direct effect of the drug on the presynaptic P-adrenoceptors located on sympathetic nerve endings (Majewski, 1983;Rump & Majewski, 1987); these presynaptic fi-adrenoceptors seem to belong to the #2-subtype (Brodde et al, 1988). The lipid mobilizing effect of yohimbine may be explained through sympathetic activation, CX2-adrenoceptor blockade on fat cells, or both.…”

Section: Discussionmentioning

confidence: 99%

Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects

Valet¹,

Taouis²,

Tran³

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

provoked an equivalent increase in plasma non-esterified fatty acids (+ 100%). Procaterol, but not yohimbine, induced hyperglycaemia (+ 120%). Plasma insulin was weakly enhanced by yohimbine (+ 120%) as compared to the increase given by procaterol (+ 500%). 4 Both drugs stimulated sympathetic nervous system activity, as indicated by the increased plasma noradrenaline concentration, but only yohimbine increased the plasma adrenaline level. 5 Cardiovascular measurements indicated that procaterol strongly enhances heart rate and transiently decreases mean blood pressure. Yohimbine exhibits a weaker effect on heart rate and slightly increases mean blood pressure. 6 The present work clearly indicates that lipid mobilization is enhanced during fasting in the dog by selective fl2-adrenoceptor stimulation or by Cc2-adrenoceptor blockade. This enhanced lipolytic effect may result either from a direct action of the drugs on the adrenoceptors of fat cells or from an activation of the sympathetic nervous system. Procaterol suffers major limitations since it strongly increases heart rate, immunoreactive insulin and glycaemia. On the other hand, yohimbine induces only minor modifications both in cardiovascular and endocrinological parameters.

show abstract

Section: Discussionmentioning

confidence: 99%

Lipomobilizing effects of procaterol and yohimbine in the conscious dog: comparison of endocrinological, metabolic and cardiovascular effects

Valet¹,

Taouis²,

Tran³

et al. 1989

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…89 Although it is possible that blockade of ␤ 2 -ARs or other carvedilol characteristics could have provided small incremental benefit, because of the likely difference in degree of ␤ 1 -AR blockade, it is not possible to conclude that the ␤ 1 /␤ 2 /␣ 1 -blocker carvedilol has superior efficacy to the ␤ 1 -selective compound metoprolol. 92 Studies comparing ␤-adrenergic blocking agents should document equivalent degrees of ␤ 1 -AR blockade by measurement of exercise heart rate responses 93 or use doses and formulations of each agent that have been successful against placebo in other trials.…”

Section: Era Of Phase 3 ␤-Blocker Clinical Trials 1993-2003mentioning

confidence: 99%

Treatment of Chronic Heart Failure With β-Adrenergic Receptor Antagonists

Bristow

2011

Circulation Research

151

View full text Add to dashboard Cite

ReviewTranslational Success Stories highlight how basic discoveries have led to clinical advances (such as the use of new drugs or diagnostic modalities in patients). This initiative reflects the renewed emphasis of our journal on translational research. It is hoped that these articles will stimulate efforts to translate basic insights into clinical practice. Treatment of Chronic Heart Failure With ␤-AdrenergicReceptor Antagonists A Convergence of Receptor Pharmacology and Clinical CardiologyMichael R. BristowAbstract: Despite the absence of a systematic development plan, ␤-blockers have reached the top tier of medical therapies for chronic heart failure. The successful outcome was due to the many dedicated investigators who produced, over a 30-year period, increasing evidence that ␤-blocking agents should or actually did improve the natural history of dilated cardiomyopathies and heart failure. It took 20 years for supportive evidence to become undeniable, at which time in 1993 the formidable drug development resources of large pharmaceutical companies were deployed into Phase 3 trials. Success then came relatively quickly, and within 8 years multiple agents were on the market in the United States and Europe. Importantly, there is ample room to improve antiadrenergic therapy, through novel approaches exploiting the nuances of receptor biology and/or intracellular signaling, as well as through pharmacogenetic targeting. (Circ Res. 2011;109:1176-1194.)Key Words: heart failure Ⅲ adrenergic receptors Ⅲ ␤-blockers Ⅲ norepinephrine Ⅲ drug development "I love it when a plan comes together" -Colonel John "Hannibal" Smith, The A-Team ␤ -Adrenergic blocking agents are now considered firstline therapy for chronic heart failure. 2 Between 1971 and 2001, ␤-blockers as a drug class went from contraindicated to being universally declared a highly effective new therapy for chronic heart failure with systolic dysfunction. As depicted in Figure 1, this 180-degree turn required the convergence of initially disconnected lines of basic and clinical investigation, none of which was systematically planned by the usual purveyors of drug development, large pharmaceutical companies. However, as for the typical outcome of Colonel Hannibal Smith's unconventional and dubious tactical schemes, 1 the end result was highly successful. This review provides some of the historical highlights, summarizes current knowledge, and provides thoughts on the future of ␤-blocker and antiadrenergic therapy. Historical Highlights Discovery of Adrenergic ReceptorsIn 1948, Raymond Ahlquist reported evidence for two types of adrenergic receptors, 3 which, "for convenience," he termed alpha and beta. The evidence was based on 2 distinct rank orders of agonist potency for a variety of pharmacological responses, plus the ability to inhibit the vasoconstrictor or uterine contraction responses of the ␣ group, with 3 different compounds (dibenamine, ergotoxine, or tolazoline) that would later be termed ␣-blocking agents. At the time of Ahlquist's landmark work, the...

show abstract

“…Procaterol treatment increased heart rate by [10][11][12][13][14][15] beats/min after 12-24 hours. During further treatment, heart rate declined slowly and reached predrug levels about 2-3 days after withdrawal of procaterol.…”

mentioning

confidence: 96%