β 2 -Adrenoceptor agonist activity of higenamine.

Autor: Hudzik TJ; Department of Research, GlaxoSmithKline, 1250 S. Collegeville Rd, Collegeville, PA, 1926, USA., Patel M; Department of Research, GlaxoSmithKline, Gunnels Wood Rd, Stevenage, SG1 2NY, UK., Brown A; Department of Research, GlaxoSmithKline, Gunnels Wood Rd, Stevenage, SG1 2NY, UK.
Jazyk: angličtina
Zdroj: Drug testing and analysis [Drug Test Anal] 2021 Feb; Vol. 13 (2), pp. 261-267. Date of Electronic Publication: 2021 Jan 12.
DOI: 10.1002/dta.2992
Abstrakt: Higenamine was included in the World Anti-Doping Agency (WADA) Prohibited Substances and Methods List as a β 2 -adrenoceptor agonist in 2017, thereby resulting in its prohibition both in and out of competition. The present mini review describes the physiology and pharmacology of adrenoceptors, summarizes the literature addressing the mechanism of action of higenamine and extends these findings with previously unpublished in silico and in vitro work. Studies conducted in isolated in vitro systems, whole-animal preparations and a small number of clinical studies suggest that higenamine acts in part as a β 2 -adrenoceptor agonist. In silico predictive tools indicated that higenamine and possibly a metabolite have a high probability of interacting with the β 2 -receptor as an agonist. Stable expression of human β 2 -receptors in Chinese hamster ovary (CHO) cells to measure agonist activity not only confirmed the activity of higenamine at β 2 but also closely agreed with the in silico prediction of potency for this compound. These data confirm and extend literature findings supporting the inclusion of higenamine in the Prohibited List.
(© 2020 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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