Adrenergics and Adrenergic‐Blocking Agents

Abstract

This chapter reviews the drugs currently available in the United States that exert their therapeutic effects through actions on α‐ and β‐adrenoceptors and biosynthesis, release, and processing of the neurotransmitter norepinephrine. Included in the review are drugs acting as selective and nonselective agonists and antagonists at both α‐ and β‐adrenoceptors, as well as drugs that interfere with norepinephrine biosynthesis and release. Therapeutic categories include antihypertensives, bronchodilators, antiglaucoma agents, vasopressors, and nasal decongestants. Structure‐activity relationships are reviewed as are the structure and function of various adrenoceptors. Briefly covered is the metabolism of representative drugs in each structural class as well as recent developments in approaches to new drugs in the areas of selective α 1A ‐antagonists for treatment of prostatic hypertrophy and selective β 3 ‐agonists for treatment of obesity and diabetes.

β‐Cardiotoxin: a new three‐finger toxin from Ophiophagus hannah (king cobra) venom with beta‐blocker activity

“…Owing to the presence of ␤-ARs in various noncardiac tissues, beta-blockers have also been used to treat conditions like, migraine, essential tremor, situational anxiety, alcohol withdrawal, hyperparathyroidism, glaucoma, portal hypertension, and gastrointestinal bleeding (33). Most of the beta-blockers in clinical use currently are small molecules belonging to the aryloxypropanolamine class (34). Although they are widely used, physicians have encountered several problems associated with the currently available beta-blockers.…”

“…For example, in a clinical trial using the D-enantiomer of the widely used beta-blocker sotalol, it was reported that the mortality increased by 65% compared to placebo (35). Many beta-blockers exhibit varying levels of lipophilicity and so have the ability to cross membrane barriers and reach the central nervous system, causing adverse effects like hallucinations and insomnia (34). Some beta-blockers are shown to increase insulin resistance and raise the risk of diabetes (36).…”

Synthesis of new compounds of the aryloxyaminopropanol type and their HPLC enantioseparation

“…In many papers, compounds with isopropyl and tert-butyl group in the hydrophilic part of molecule are active beta-adrenolytics (Čižmáriková & Račanská, 1998;Bruchatá & Čižmáriková, 2010;Kečkéšová & Sedlárová, 2010). Lower beta-adrenolytic activity was observed in the compounds with other alkyl groups such as isobutyl and diethyl groups (Griffith, 2003). The large variety of different aromatic rings and substituents on nitrogen atom leads to compounds with combined pharmacological properties with affinity to both types of adrenergic receptor, α and β (Bruchatá & Čižmáriková, 2010).…”

Evaluation of the Potential for Pharmacodynamic and Pharmacokinetic Drug Interactions Between Selegiline Transdermal System and Two Sympathomimetic Agents (Pseudoephedrine and Phenylpropanolamine) in Healthy Volunteers

“…Pseudoephedrine (PSE) and phenylpropanolamine (PPA) are mixed‐acting sympathomimetic amines that have been used commonly as decongestants in the treatment of coughs and colds 10 – 14 . The effectiveness of PSE and PPA as decongestants is specifically related to the activation of α‐adrenergic receptors in the nasal mucosa, resulting in vasoconstriction, reduced blood flow, decreased mucosal edema, and, ultimately, improved nasal patency 15 , 16 . At mucosal sympathetic nerve endings, these agents directly stimulate adrenergic receptors (direct action) and displace norepinephrine from neuronal storage sites (indirect action).…”

“…[10][11][12][13][14] The effectiveness of PSE and PPA as decongestants is specifically related to the activation of α-adrenergic receptors in the nasal mucosa, resulting in vasoconstriction, reduced blood flow, decreased mucosal edema, and, ultimately, improved nasal patency. 15,16 At mucosal sympathetic nerve endings, these agents directly stimulate adrenergic receptors (direct action) and displace norepinephrine from neuronal storage sites (indirect action). However, these same actions can also have a generalized effect on the peripheral cardiovascular system that can be exaggerated in the presence of an MAOI.…”