Agonist (pharmacology)

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Dose-response curves of agonists that lead to full (full agonist) or partial activation of a receptor (partial agonist).

As agonist (from ancient Greek αγωνιστής agonistes "the employed, actor, leading") is in the Pharmacology a substance ( ligand hereinafter), which by occupying a receptor , the signal transduction in the associated cell activated. An agonist can be an endogenous substance (e.g. a hormone or a neurotransmitter ) or a non-endogenous active ingredient that imitates or replaces a certain messenger substance . Chemical compounds that bind to a receptor, but do not activate it, and thus block and inhibit, are called antagonists .

On the basis of the degree of activation, a distinction can be made between a full agonist and a partial agonist . Inverse agonists , which lead to an inactivation of a spontaneously active receptor and thus show an effect that is too full and that of partial agonists, are not assigned to the agonists.

The extent to which a receptor is activated does not only depend on the properties of the ligand, but is also dependent on the extent to which the receptor is expressed in the examined cells or in the examined tissue. In addition, some agonists are able to activate different signaling pathways to different degrees via the same receptor and thus - depending on the signal examined - to produce differently pronounced effects. Depending on the signal examined, they can be full agonists, partial agonists, silent antagonists or inverse agonists at the same time . Such agonists are also referred to as proteinaceous or functionally selective .

Examples

The following table shows examples of receptors or their subtypes and their agonists at the orthosteric binding site.

Receptors and their agonists
receptor Subtype Agonist
endogenous; exogenous
Acetylcholine receptors M 1-5 Acetylcholine ; Carbachol , muscarin
N 1-2 Acetylcholine; nicotine
Adrenoceptors α 1A, B, D Adrenaline , noradrenaline ; Phenylephrine
α 2A-C Adrenaline, noradrenaline; Clonidine
β 1-3 Adrenaline; Isoprenaline
Dopamine receptors D 1-5 Dopamine
Histamine receptors H 1-4 histamine
Opioid receptors μ 1.2 β-endorphin ; Casein , morphine V , buprenorphine P , dermorphine
κ 1-3 Dynorphins ; Enadolin
δ 1.2 β-endorphins, enkephalins , deltorphins
Serotonin receptors 5-HT 1A-F , 5-HT 5A , 5-HT 7 Serotonin ; 5-carboxamidotryptamine
5-HT 2A-C Serotonin; α-methylserotonin
5-HT 3 Serotonin; 2-methylserotonin
5-HT 4 Serotonin; 5-methoxytryptamine
5-HT 6 Serotonin; EMDT
5-HT 7 Serotonin; N-methylserotonin
Table legend
  1. ↑ endogenous = mediator in the human body, exogenous = exogenous transmitter substance; V = full agonist, P = partial agonist, Ak = particularly high agonistic activity; FS = dedicated functional selectivity is known; Sp = subtype specific (so far known); rN, sN = eponymous for the receptor or subtype (for exogenous agonists or non-trivial cases); Af = extremely affine; Rvi = radioagonist , use in vivo ; Rvt = predominant use in vitro (see also PET , tracer , binding study )

literature

Individual evidence

  1. ↑ D. Hoyer, HW Boddeke: Partial agonists, full agonists, antagonists: dilemmas of definition. In: Trends Pharmacol. Sci. 14, 1993, pp. 270-275. PMID 8105597 .
  2. ↑ T. Kenakin: Inverse, protean, and ligand-selective agonism: matters of receptor conformation. In: FASEB J . 15, 2001, pp. 598-611. PMID 11259378 .
  3. ↑ JD Urban, WP Clarke, M. von Zastrow, DE Nichols, B. Kobilka, H. Weinstein, JA Javitch, BL Roth, A. Christopoulos, PM Sexton, KJ Miller, M. Spedding & RB Mailman: Functional selectivity and classical concepts of quantitative pharmacology. In: J. Pharmacol. Exp. Ther. 320, 2007, pp. 1-13. PMID 16803859 .
  4. ↑ J62019 Dermorphin. ( Memento from August 16, 2015 in the web archive archive.today ) alfa.com
  5. ^ P. Svenningsson et al. a .: Biochemical and behavioral evidence for antidepressant-like effects of 5-HT6 receptor stimulation. In: J Neurosci. 27 (15), 2007, pp. 4201-4209. PMID 17428998 .