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Clinical Autonomic Research : Official... Aug 2010We tested whether the inter-individual variability in alpha-adrenergic support of blood pressure plays a critical role in the sex differences in tonic support of blood... (Comparative Study)
Comparative Study
We tested whether the inter-individual variability in alpha-adrenergic support of blood pressure plays a critical role in the sex differences in tonic support of blood pressure by the autonomic nervous system. Blockade of the alpha-adrenergic receptors was achieved via phentolamine and showed a smaller (P < 0.05) decrease in blood pressure in women compared to men, implying that alpha-adrenergic support of blood pressure is less in women than in men.
Topics: Adrenergic Agents; Adult; Blood Pressure; Female; Humans; Male; Phentolamine; Sex Factors
PubMed: 20221842
DOI: 10.1007/s10286-010-0061-y -
Progress in Cardiovascular Diseases 2004Beta-adrenergic blockers are one of the most frequently prescribed cardiovascular drugs. Numerous beta-blockers are available for clinical use. Although these agents... (Review)
Review
Beta-adrenergic blockers are one of the most frequently prescribed cardiovascular drugs. Numerous beta-blockers are available for clinical use. Although these agents differ substantially, it is not clear whether (and which) differences are clinically relevant. Most of the important differences among agents reflect the relative specificity for beta1-, beta2-, and alpha-adrenergic receptors. Selection of a particular agent and target dose is probably best guided by available trial data, even though data are limited. Nonselective agents (with or without alpha-blocking properties) devoid of intrinsic sympathetic activity (ISA) are most appropriate postinfarction. Evidence exists demonstrating a mortality benefit postinfarction for propranolol, timolol, metoprolol, and, in the presence of left ventricular dysfunction, carvedilol. In the setting of heart failure, the selective agents metoprolol and bisoprolol as well as the nonselective agent carvedilol (which possesses alpha-blocking properties) have a demonstrated mortality benefit. Not all tolerated beta-blockers are associated with a survival benefit and it is probably not advisable to extrapolate benefits to all drugs with similar (although probably not identical) properties. Carvedilol may possess advantages over other beta-blockers and a possible survival advantage, suggested by the recent Carvedilol or Metoprolol European Trial (COMET), although these findings are not universally accepted. Ultimately, selection of a specific agent avoids obvious contraindications and uses trial data to guide selection and dose as long as side effects are absent or tolerable.
Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Heart Failure; Humans; Hypertension; Randomized Controlled Trials as Topic
PubMed: 15517513
DOI: 10.1016/j.pcad.2004.04.004 -
Journal of Clinical Pharmacology Mar 1986Esmolol is an ultra-short-acting beta-adrenergic blocking agent that possesses minimal partial agonist activity or direct membrane depressant activity. The short...
Esmolol is an ultra-short-acting beta-adrenergic blocking agent that possesses minimal partial agonist activity or direct membrane depressant activity. The short duration of action of esmolol is attributable to rapid enzymatic hydrolysis by red blood cell esterases, forming ASL-8123 and methanol. Experiments in the constant-flow-perfused isolated canine hindlimb indicate that therapeutic (beta blocking) doses of esmolol lack direct vascular effects and alpha-adrenergic blocking activity and that therapeutic doses do not interfere with vascoconstrictor effects of peripheral sympathetic nerve stimulation. Esmolol produces cardiac electrophysiologic and hemodynamic effects consistent with those of beta blockade. Specifically, esmolol decreases heart rate, depresses atrioventricular nodal conduction, and decreases determinants of myocardial oxygen demand. The beneficial antiarrhythmic and infarct-size limiting effects of esmolol have been demonstrated in several experimental models. Whereas beta blockers in general are effective in settings of supraventricular arrhythmias, sinus tachycardia, and myocardial ischemia, esmolol provides the added dimension of "titratability." Thus, the short duration of action of esmolol allows for very rapid titration to a preferred steady-state level of beta blockade; rapid adjustment to different steady-state levels of beta blockade, as may be required by changing status of the patient, and rapid disappearance of beta blockade following discontinuation of esmolol infusion, should this be necessary in the event of deleterious cardiac hemodynamic effects. Thus, esmolol is ideally suited for use in the treatment of patients in whom beta blockade is desirable, but in whom level of beta blockade must be very carefully modulated.
Topics: Adrenergic beta-Antagonists; Anesthesia; Animals; Anti-Arrhythmia Agents; Catecholamines; Coronary Circulation; Dogs; Heart; Heart Conduction System; Hemodynamics; Hindlimb; Kinetics; Myocardial Infarction; Oxygen Consumption; Propanolamines; Regional Blood Flow; Tissue Distribution
PubMed: 2870084
DOI: 10.1002/j.1552-4604.1986.tb02985.x -
Nihon Yakurigaku Zasshi. Folia... Nov 2001Catecholamine, dopamine, serotonine (5HT) and neuronal histamine are anorectic monoamines and act as anorectic neurotransmitters. The anorectic agents as modulators of... (Review)
Review
Catecholamine, dopamine, serotonine (5HT) and neuronal histamine are anorectic monoamines and act as anorectic neurotransmitters. The anorectic agents as modulators of these monoamines inhibit appetite by activating release together with suppressing reuptake of those monoamines. The anorectic agents were classified in clinical use into either alpha 1, beta-adrenergic receptor agonists or 5HT-receptor agonist. Dexfenfluramine, a 5HT-receptor agonist, was inhibited in clinical use because of its cardiac complications including pulmonary hypertension and valvelar disease. Mazindol is an adrenergic agonist and the solitary anti-obesity drug used clinically in Japan. Sibutramine shows the effects of both beta-adrenergic and serotonergic receptor agonists. Sibutramine induces not only appetite suppression but also acceleration of peripheral energy expenditure. No histaminergic anorectics have been employed in the clinical situation to date. L-Histizine, precursor amino acid of endogenous neuronal histamine, is useful for suppression of food intake, lipolytic acceleration of peripheral adipose tissues and enhanced energy expenditure in both animals and humans. L-Histizine thus inspires development of more effective and safer anorectics that can be used without suffering from the rebound phenomenon of body weight.
Topics: Adrenergic Agents; Animals; Appetite Depressants; Histamine Agents; Humans; Serotonin Agents
PubMed: 11729632
DOI: 10.1254/fpj.118.303 -
Neuroscience 2005Adrenergic signaling regulates the timing of sleep states and sleep state-dependent changes in muscle tone. Recent studies indicate a possible role for noradrenergic...
Adrenergic signaling regulates the timing of sleep states and sleep state-dependent changes in muscle tone. Recent studies indicate a possible role for noradrenergic transmission in the wake-promoting action of modafinil, a widely used agent for the treatment of excessive sleepiness. We now report that noradrenergic projections from the locus coeruleus to the forebrain are not necessary for the wake-promoting action of modafinil. The efficacy of modafinil was maintained after treatment of C57BL/6 mice with N-(2-chloroethyl)-N-ethyl 2-bromobenzylamine (DSP-4), which eliminates all noradrenaline transporter-bearing forebrain noradrenergic projections. However, the necessity for adrenergic receptors in the wake-promoting action of modafinil was demonstrated by the observation that the adrenergic antagonist terazosin suppressed the response to modafinil in DSP-4 treated mice. The wake-promoting efficacy of modafinil was also blunted by the dopamine autoreceptor agonist quinpirole. These findings implicate non-noradrenergic, dopamine-dependent adrenergic signaling in the wake-promoting mechanism of modafinil. The anatomical specificity of these dopaminergic-adrenergic interactions, which are present in forebrain areas that regulate sleep timing but not in brain stem areas that regulate sleep state-dependent changes in muscle tone, may explain why modafinil effectively treats excessive daytime sleepiness in narcolepsy but fails to prevent the loss of muscle tone that occurs in narcoleptic patients during cataplexy.
Topics: Adrenergic Agents; Animals; Benzhydryl Compounds; Benzylamines; Brain; Central Nervous System Stimulants; Dopamine; Dopamine Agonists; Fluoxetine; Male; Mice; Modafinil; Narcolepsy; Neural Pathways; Norepinephrine; Quinpirole; Sleep; Wakefulness
PubMed: 15857707
DOI: 10.1016/j.neuroscience.2005.02.003 -
Nihon Rinsho. Japanese Journal of... Aug 1996It has been reported that beta-blocker treatment reduces the incidence of sudden cardiac death after myocardial infarction, possibly due to antiischemic and... (Review)
Review
It has been reported that beta-blocker treatment reduces the incidence of sudden cardiac death after myocardial infarction, possibly due to antiischemic and antiarrhythmic effects. Beta adrenoceptor blocking drugs are administered, as an antiarrhythmic agent in patients with hyperthyroidism, atrial fibrillation, atrial flutter and ventricular tachyarrhythmias. Even low dose beta-blocker administration reduces the incidence of PVC's. Beta blockers are expected to decrease the ventricular rate of persistent tachyarrhythmias resulting from excessive cardiac sympathetic tone. Existence of denervated areas in myocardium in the cases of ventricular tachyarrhythmias may be shown in the cardiac scintigram as abnormal myocardial uptake of 123I-MIBG.
Topics: Adrenergic beta-Antagonists; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Female; Humans; Male; Middle Aged
PubMed: 8810786
DOI: No ID Found -
Journal of Medical Toxicology :... Dec 2014The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search... (Review)
Review
The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.
Topics: Adrenergic alpha-2 Receptor Agonists; Alcoholism; Clonidine; Dexmedetomidine; Humans; Opioid-Related Disorders; Substance Withdrawal Syndrome; Tobacco Use Disorder
PubMed: 25238670
DOI: 10.1007/s13181-014-0430-3 -
Journal of Hypertension Sep 2010The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in... (Review)
Review
The role of alpha-1 adrenoceptor antagonists (alpha-blockers) in the management of hypertension continues to evolve. Recent data support their use as add-on therapy in uncontrolled hypertension when used in combination with all other major classes of antihypertensive drug and there is increasing evidence suggesting that they have modest but significant beneficial effects on lipid and glucose metabolism. The availability of extended-release formulations has contributed to an excellent tolerability profile. New data from an observational analysis of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) suggest that doxazosin gastrointestinal therapeutic system (GITS) used as a third-line antihypertensive agent lowered blood pressure and caused modest reductions in plasma lipids. Furthermore, use of doxazosin in ASCOT was not associated with an increased risk of heart failure, in contrast to the earlier finding of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Overall, currently available data support the use of alpha-blockers as safe, well tolerated and effective add-on antihypertensive drugs, which have additional favourable metabolic effects.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Clinical Trials as Topic; Doxazosin; Drug Therapy, Combination; Heart Failure; Humans; Hypertension; Lipids; Myocardial Infarction; Practice Guidelines as Topic
PubMed: 20543713
DOI: 10.1097/HJH.0b013e32833b912c -
Cells Jan 2023Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β...
Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β adrenergic receptor (βAR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is a single-molecule, dual pharmacology agent combining muscarinic antagonist and βAR agonist functions, currently in development as a COPD therapeutic. In precision-cut human lung slices (hPCLS), we investigated the bronchoprotective effect of navafenterol against two non-muscarinic contractile agonists, histamine and thromboxane A (TxA) analog (U46619). Navafenterol pre-treatment significantly attenuated histamine-induced bronchoconstriction and βAR antagonist propranolol reversed this inhibitory effect. TxA analog-induced bronchoconstriction was attenuated by navafenterol pre-treatment, albeit to a lesser magnitude than that of histamine-induced bronchoconstriction. Propranolol completely reversed the inhibitory effect of navafenterol on TxA analog-induced bronchoconstriction. In the presence of histamine or TxA analog, navafenterol exhibits bronchoprotective effect in human airways and it is primarily mediated by βAR agonism of navafenterol.
Topics: Humans; Bronchodilator Agents; Muscarinic Antagonists; Histamine; Propranolol; Lung; Pulmonary Disease, Chronic Obstructive; Receptors, Muscarinic; Adrenergic Agonists
PubMed: 36672178
DOI: 10.3390/cells12020240 -
Vascular Health and Risk Management 2006Nebivolol is a novel beta1-blocker with a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and a nitric oxide... (Review)
Review
Nebivolol is a novel beta1-blocker with a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and a nitric oxide (NO)-potentiating, vasodilatory effect that is unique among beta-blockers currently available to clinicians (nebivolol is approved in Europe and is currently under review in the US). A NO-potentiating agent such as nebivolol may have an important role in hypertensive populations with reduced endothelial function such as diabetics, African-Americans and those with vascular disease. Nebivolol is a racemic mixture with beta-blocker activity residing in the d-isomer; in contrast, l-nebivolol is far more potent in facilitating NO release. Nebivolol is unique among beta-blockers in that, at doses < 10 mg, it does not inhibit the increase in heart rate normally seen with exercise. The efficacy ofnebivolol has been tested successfully in clinical trials against other agents including other beta-blockers, angiotensin-converting enzyme-inhibitors and calcium channel antagonists in patients with hypertension, angina, and congestive heart failure. The tolerability of nebivolol has been shown to be superior to that of atenolol and metoprolol. In controlled clinical trials, nebivolol has a side effect profile that is similar to placebo, in particular as it relates to fatigue and sexual dysfunction. This article will review published clinical data regarding this cardioselective beta-blocker.
Topics: Adrenergic beta-Antagonists; Benzopyrans; Blood Pressure; Cardiovascular Diseases; Endothelium, Vascular; Ethanolamines; Heart Rate; Humans; Hypertension; Nebivolol; Nitric Oxide; Vasodilation
PubMed: 17326335
DOI: 10.2147/vhrm.2006.2.3.303