IUPHAR/BPS Guide to Pharmacology CITE
https://doi.org/10.2218/gtopdb/F4/2025.3

Adrenoceptors in GtoPdb v.2025.3



Jillian G. Baker1, Poornima Balaji2, Richard A. Bond3, David B. Bylund4, Douglas C. Eikenburg5, Robert M. Graham2, J. Paul Hieble6, Rebecca Hills7, Martin C. Michel8, Kenneth P. Minneman9, Sergio Parra3, Dianne Perez10 and Roger J. Summers11
  1. University of Nottingham, UK
  2. Victor Chang Cardiac Research Institute, Australia
  3. University of Houston, USA
  4. University of Nebraska, USA
  5. University of Houston College of Pharmacy, USA
  6. GlaxoSmithKline, USA
  7. University of Edinburgh, UK
  8. Johannes Gutenberg University, Germany
  9. Emory University, USA
  10. Cleveland Clinic Lerner Research Institute, USA
  11. Monash University, Australia


Abstract

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [116, 324].

Adrenoceptors, α1
The three α1-adrenoceptor subtypes α1A, α1B and α1D are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. -(-)phenylephrine, methoxamine and cirazoline are agonists and prazosin and doxazosin antagonists considered selective for α1- relative to α2-adrenoceptors. [3H]prazosin and HEAT (BE2254) (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy FLprazosin- QAPB) are used to examine cellular localisation of α1-adrenoceptors. α1-Adrenoceptor agonists are used as nasal decongestants; antagonists to treat symptoms of benign prostatic hyperplasia (alfuzosin, doxazosin, terazosin, tamsulosin and silodosin, with the last two compounds being α1A-adrenoceptor selective and claiming to relax bladder neck tone with less hypotension); and to a lesser extent hypertension (doxazosin, terazosin). The α1- and β2-adrenoceptor antagonist carvedilol is used to treat congestive heart failure, although the contribution of α1-adrenoceptor blockade to the therapeutic effect is unclear. Several anti-depressants and anti-psychotic drugs are α1-adrenoceptor antagonists contributing to side effects such as orthostatic hypotension.

Adrenoceptors, α2
The three α2-adrenoceptor subtypes α2A, α2B and α2C are activated by (-)-adrenaline and with lower potency by (-)-noradrenaline. brimonidine (UK14304) and talipexole are agonists and rauwolscine and yohimbine antagonists selective for α2- relative to α1-adrenoceptors. [3H]rauwolscine, [3H]brimonidine (UK14304) and [3H]RX821002 are relatively selective radioligands. There are species variations in the pharmacology of the α2A-adrenoceptor. Multiple mutations of α2-adrenoceptors have been described, some associated with alterations in function. Presynaptic α2-adrenoceptors regulate many functions in the nervous system. The α2-adrenoceptor agonists clonidine, guanabenz and brimonidine (UK14304) affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation. clonidine is an anti-hypertensive (relatively little used) and counteracts opioid withdrawal. dexmedetomidine (also xylazine) is increasingly used as a sedative and analgesic in human [64] and veterinary medicine and has sympatholytic and anxiolytic properties. The α2-adrenoceptor antagonist mirtazapine is used as an anti-depressant. The α2B subtype appears to be involved in neurotransmission in the spinal cord and α2C in regulating catecholamine release from adrenal chromaffin cells. Although subtype-selective antagonists have been developed, none are used clinically and they remain experimental tools.

Adrenoceptors, β
The three β-adrenoceptor subtypes β1, β2 and β3 are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. Isoprenaline is selective for β-adrenoceptors relative to α1- and α2-adrenoceptors, while propranolol (pKi 8.2-9.2) and cyanopindolol (pKi 10.0-11.0) are relatively selective antagonists for β1- and β2- relative to β3-adrenoceptors. (-)-noradrenaline, xamoterol and (-)-Ro 363 show selectivity for β1- relative to β2-adrenoceptors. Pharmacological differences exist between human and mouse β3-adrenoceptors, and the 'rodent selective' agonists BRL 37344 and CL316243 have low efficacy at the human β3-adrenoceptor whereas CGP 12177 (low potency) and L 755507 activate human β3-adrenoceptors [88]. β3-Adrenoceptors are resistant to blockade by propranolol, but can be blocked by high concentrations of bupranolol. SR59230A has reasonably high affinity at β3-adrenoceptors, but does not discriminate between the three β- subtypes [520] whereas L-748337 is more selective. [125I]-cyanopindolol, [125I]-hydroxy benzylpindolol and [3H]-alprenolol are high affinity radioligands that label β1- and β2- adrenoceptors and β3-adrenoceptors can be labelled with higher concentrations (nM) of [125I]-cyanopindolol together with β1- and β2-adrenoceptor antagonists. Fluorescent ligands such as BODIPY-TMR-CGP12177 can be used to track β-adrenoceptors at the cellular level [8]. Somewhat selective β1-adrenoceptor agonists (denopamine, dobutamine) are used short term to treat cardiogenic shock but, chronically, reduce survival. β1-Adrenoceptor-preferring antagonists are used to treat cardiac arrhythmias (atenolol, bisoprolol, esmolol) and cardiac failure (metoprolol, nebivolol) but also in combination with other treatments to treat hypertension (atenolol, betaxolol, bisoprolol, metoprolol and nebivolol) [820]. Cardiac failure is also treated with carvedilol that blocks β1- and β2-adrenoceptors, as well as α1-adrenoceptors. Short (salbutamol, terbutaline) and long (formoterol, salmeterol) acting β2-adrenoceptor-selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation β-adrenoceptor antagonists (propranolol) block both β1- and β2-adrenoceptors and there are no β2-adrenoceptor-selective antagonists used therapeutically. The β3-adrenoceptor agonist mirabegron is used to control overactive bladder syndrome. There is evidence to suggest that β-adrenoceptor antagonists can reduce metastasis in certain types of cancer [327].

Contents

This is a citation summary for Adrenoceptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts. For further details see [108].

Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

Adrenoceptors
https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=4
Introduction to Adrenoceptors
https://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=4
    Receptors
            α1A-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=22
            α1B-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=23
            α1D-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=24
            α2A-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=25
            α2B-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=26
            α2C-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=27
            β1-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=28
            β2-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=29
            β3-adrenoceptor
            https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=30

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