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Molecules (Basel, Switzerland) Jan 2021β-adrenergic antagonists (β-blockers) with at least one chiral center are an exceedingly important class of drugs used mostly to treat cardiovascular diseases. At... (Review)
Review
β-adrenergic antagonists (β-blockers) with at least one chiral center are an exceedingly important class of drugs used mostly to treat cardiovascular diseases. At least 70 β-blockers have been investigated in history. However, only a few β-blockers, e.g., timolol, are clinically marketed as an optically pure enantiomer. Therefore, the separation of racemates of β-blockers is essential both in the laboratory and industry. Many approaches have been explored to obtain the single enantiomeric β-blocker, including high performance liquid chromatography, supercritical fluid chromatography and simulated moving bed chromatography. In this article, a review is presented on different chromatographic methods applied for the enantioseparation of β-blockers, covering high performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC) and simulated moving bed chromatography (SMB).
Topics: Adrenergic beta-Antagonists; Chromatography, High Pressure Liquid; Chromatography, Supercritical Fluid; Stereoisomerism
PubMed: 33477385
DOI: 10.3390/molecules26020468 -
Cardiology 2018The pharmacologic treatment of arrhythmias has seen little advance over the past few years. Physicians treating life threatening or hemodynamically destabilizing... (Review)
Review
The pharmacologic treatment of arrhythmias has seen little advance over the past few years. Physicians treating life threatening or hemodynamically destabilizing arrhythmias depend almost entirely on intravenous (IV) amiodarone. This is regrettable due to the multiple toxicities of amiodarone and its long half-life. Once administered, it is a therapeutic commitment to long-term therapy. Given the very long terminal elimination half-life, treatment with amiodarone may interfere with baseline electrophysiologic studies and ablation procedures. Additionally, the side effect profile can be consequential, even with brief periods of treatment. Currently, sotalol, like amiodarone, is available in both IV and oral formulations, facilitating their use in emergency situations. IV sotalol has a rapid onset of action with linear pharmacokinetics. While sotalol's efficacy has mostly been evaluated in small clinical trials, 2 recent meta-analysis have been informative as to the utility of sotalol. Sotalol has similar efficacy as amiodarone, but has much more favorable adverse event profile. IV sotalol has been underutilized and could offer advantage in the treatment of AF for rate and rhythm control, as well in the pediatrics for treatment of supraventricular arrhythmias often resistant to other therapies.
Topics: Administration, Intravenous; Adrenergic beta-Antagonists; Amiodarone; Arrhythmias, Cardiac; Dose-Response Relationship, Drug; Humans; Sotalol
PubMed: 30016794
DOI: 10.1159/000490759 -
Indian Journal of Ophthalmology Jan 2011Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only... (Review)
Review
Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications.
Topics: Administration, Topical; Adrenergic Antagonists; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Clinical Trials as Topic; Evidence-Based Medicine; Glaucoma; Humans; Neuroprotective Agents; Prostaglandins
PubMed: 21150020
DOI: 10.4103/0301-4738.73700 -
Drugs Mar 2014Hypertensive disorders represent major causes of pregnancy-related maternal mortality worldwide. Similar to the non-pregnant population, hypertension is the most common... (Review)
Review
Hypertensive disorders represent major causes of pregnancy-related maternal mortality worldwide. Similar to the non-pregnant population, hypertension is the most common medical disorder encountered during pregnancy and is estimated to occur in about 6-8 % of pregnancies. A recent report highlighted hypertensive disorders as one of the major causes of pregnancy-related maternal deaths in the USA, accounting for 579 (12.3 %) of the 4,693 maternal deaths that occurred between 1998 and 2005. In low-income and middle-income countries, preeclampsia and its convulsive form, eclampsia, are associated with 10-15 % of direct maternal deaths. The optimal timing and choice of therapy for hypertensive pregnancy disorders involves carefully weighing the risk-versus-benefit ratio for each individual patient, with an overall goal of improving maternal and fetal outcomes. In this review, we have compared and contrasted the recommendations from different treatment guidelines and outlined some newer perspectives on management. We aim to provide a clinically oriented guide to the drug treatment of hypertension in pregnancy.
Topics: Adrenergic Antagonists; Adrenergic alpha-2 Receptor Agonists; Antihypertensive Agents; Blood Pressure Determination; Calcium Channel Blockers; Diuretics; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Vasodilator Agents
PubMed: 24554373
DOI: 10.1007/s40265-014-0187-7 -
The Canadian Journal of Urology Oct 2010
Topics: Adrenergic alpha-1 Receptor Antagonists; Drug Discovery; History, 20th Century; History, 21st Century; Humans; Japan; Sulfonamides; Tamsulosin; Urology
PubMed: 20974024
DOI: No ID Found -
Microbiology (Reading, England) Jul 2015Legionella pneumophila is a facultative intracellular bacterium, which upon inhalation can cause a potentially fatal pneumonia termed Legionnaires' disease. The...
Legionella pneumophila is a facultative intracellular bacterium, which upon inhalation can cause a potentially fatal pneumonia termed Legionnaires' disease. The opportunistic pathogen grows in environmental amoebae and mammalian macrophages within a unique membrane-bound compartment, the 'Legionella-containing vacuole'. Bacteria are exposed to many environmental cues including small signalling molecules from eukaryotic cells. A number of pathogenic bacteria sense and respond to catecholamine hormones, such as adrenalin and noradrenalin, a process mediated via the QseBC two-component system in some bacteria. In this study, we examined the effect of adrenergic compounds on L. pneumophila, and discovered that the adrenergic receptor antagonists benoxathian, naftopidil, propranolol and labetalol, as well as the QseC sensor kinase inhibitor LED209, reduced the growth of L. pneumophila in broth or amoebae, while replication in macrophages was enhanced. Growth restriction was common to members of the genus Legionella and Mycobacterium, and was observed for L. pneumophila in the replicative but not stationary phase of the biphasic life cycle. Deletion of the L. pneumophila qseBC genes indicated that growth inhibition by adrenergics or LED209 is mediated only to a minor extent by this two-component system, implying the presence of other adrenergic sensing systems. This study identifies adrenergic molecules as novel inhibitors of extra- and intracellular growth of Legionella and reveals LED209 as a potential lead compound to combat infections with Legionella or Mycobacterium spp.
Topics: Acanthamoeba castellanii; Adrenergic Antagonists; Animals; Anti-Bacterial Agents; Cell Line; Legionella pneumophila; Macrophages; Mice; Mycobacterium
PubMed: 25873585
DOI: 10.1099/mic.0.000094 -
Clinical Interventions in Aging 2011Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for... (Review)
Review
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α(1)-adrenergic receptor antagonists. Silodosin is a new α(1)-adrenergic receptor antagonist that is selective for the α(1A)-adrenergic receptor. By antagonizing α(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α(1A)-adrenergic receptor than for the α(1B)-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α(1B)-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α(1A)-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH.
Topics: Adrenergic Antagonists; Aged; Drug-Related Side Effects and Adverse Reactions; Humans; Indoles; Male; Middle Aged; Outcome Assessment, Health Care; Prostatic Hyperplasia; Randomized Controlled Trials as Topic
PubMed: 21753871
DOI: 10.2147/CIA.S13803 -
Journal of Basic and Clinical... Jun 2021Chemokine receptor antagonists are being explored for their therapeutic potential in various disease processes. As the chemokine (C-C motif) receptor 2 (CCR2) antagonist...
OBJECTIVES
Chemokine receptor antagonists are being explored for their therapeutic potential in various disease processes. As the chemokine (C-C motif) receptor 2 (CCR2) antagonist RS504393 is known to compete with ligand binding to α-adrenoceptors, we tested a panel of 10 CCR antagonists for interactions with α-adrenoceptors to evaluate potential cardiovascular activities and side-effect profiles.
METHODS
The PRESTO-Tango β-arrestin recruitment assay was utilized to test whether the CCR antagonists interfere with α-AR activation upon stimulation with phenylephrine. Pressure myography with isolated rat resistance arteries was employed to assess their effects on phenylephrine-induced vasoconstriction. The following antagonists were tested: CCR1-BX471, BX513, BI639667; CCR2-RS504393, INCB3284; CCR3-SB328437; and CCR4-AZD2098, and C021; CCR5-Maraviroc; CCR10-BI6901. The pan-α-adrenoceptor antagonist prazosin was used as control.
RESULTS
Among the CCR antagonists tested, RS504393, BX513, and C021 inhibited phenylephrine-induced β-arrestin recruitment to α-adrenoceptor and phenylephrine-induced vasoconstriction. While RS504393 functioned as a competitive α-adrenoceptor blocker, BX513 and C021 functioned as noncompetitive α-adrenoceptor antagonists in both assay systems. Furthermore, RS504393, BX513, and C021 dose-dependently dilated arteries that were fully preconstricted with phenylephrine.
CONCLUSIONS
Our data suggest that CCR antagonists should be screened for cross-reactivity with α-adrenoceptors to exclude potential adverse cardiovascular effects when used as anti inflammatory drugs.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Phenylephrine; Prazosin; Rats; Receptors, Adrenergic, alpha-1; Receptors, Chemokine; beta-Arrestins
PubMed: 34144642
DOI: 10.1515/jbcpp-2020-0523 -
British Journal of Clinical Pharmacology 1979The clinical pharmacology of labetalol has been evaluated using pharmacological and physiological test methods. Labetalol displaces the log dose-response curves to the... (Review)
Review
The clinical pharmacology of labetalol has been evaluated using pharmacological and physiological test methods. Labetalol displaces the log dose-response curves to the right of isoprenaline-induced increases in heart rate, cardiac output and decreases in diastolic BP. The similarity in the displacements of these curves suggests labetalol has non-selective β-adrenoceptor-blocking properties. Labetalol inhibits exercise-induced increases in heart rate and systolic BP, inhibits tilt tachycardia and that associated with Valsalva's manoeuvre. Direct comparison with propranolol using the methods above have shown that the β-adrenoceptor-blocking effect of labetalol is qualitatively similar to that of propranolol but that propranolol is more potent weight for weight to the order of 4 to 6:1 propranolol:labetalol. In respect of their effects on respiratory function, labetalol and propranolol are qualitatively different; whereas propranolol increases airways resistance in equipotent β-adrenoceptor-blocking doses, labetalol does not. Labetalol displaces the log dose-response curves of phenylephrine and noradrenaline-induced increases in systolic and diastolic BPs to the right consistent with an α-adrenoceptor-blocking action. Labetalol inhibits increases in BP due to a cold stimulus, whereas propranolol does not. The combined α- and β-adrenoceptor-blocking effect of labetalol after acute and chronic administration leads to reductions in BP and peripheral resistance but little change in heart rate or cardiac output at rest. During exercise, increases in BP and heart rate are attenuated but cardiac output increases are only significantly diminished at high levels of exercise. Labetalol is less lipophylic than propranolol, with a partition coefficient of 1.2. It is almost completely metabolized being extensively conjugated.
Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Ethanolamines; Hemodynamics; Humans; Kinetics; Labetalol; Sympathetic Nervous System
PubMed: 43165
DOI: No ID Found -
Circulation Research Aug 2013Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain... (Review)
Review
Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that become activated in the syndrome to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to push the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF, along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart.
Topics: Adrenergic Antagonists; Cardiovascular Agents; Heart Failure; Humans; Receptors, Adrenergic; Renin-Angiotensin System; Sympathetic Nervous System
PubMed: 23989716
DOI: 10.1161/CIRCRESAHA.113.300308