Background:

Amibegron hydrochloride is a selective β3-adrenoceptor agonist, with an EC50 of 3.5 nM for β-adrenoceptor in rat colon; Amibegron hydrochloride has anxiolytic and antidepressant activity.

Amibegron hydrochloride (SR 58611A) is a selective β-adrenoceptor agonist, with an EC50 of 3.5 nM for β-adrenoceptor in rat colon, and 499 nM in rat uterus[1]. Amibegron hydrochloride (SR 58611A) shows little effect on β1- and β2-adrenoceptors, 5-HT uptake, noradrenaline (NA) uptake, and dopamine (DA) uptake from rat brain tissue, with IC50s of 4.6 and 1.2, 0.58, 2.5 and 3.2 μM, respectively; exhibits no effect on 5-HT1A, 5-HT2, MAO-A and MAO-B (IC50 >10 μM)[2].

Amibegron hydrochloride (SR 58611A, 0.1 to 0.3 mg/kg, i.p.) potentiates the toxicity produced by yohimbine in mice. Amibegron hydrochloride (0.6 and 2 mg/kg, i.p.) is also active in the learned helplessness model of antidepressant-like activity in rats. However, Amibegron hydrochloride exhibits no effect on the spontaneous locomotor activity of mice at up to 10 mg/kg and of rats at up tp 30 mg/kg[2]. Amibegron hydrochloride (3 and 10 mg/kg, p.o.) increases the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas such as cortex, hippocampus, hypothalamus, striatum. In addition, Amibegron hydrochloride (10 mg/kg, p.o.) promotes the release of 5-HT in rat prefrontal cortex. Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.) does not affect the activity of serotonergic neurons in the rat dorsal raphe nucleus[3].

参考文献:
[1]. Bianchetti A, et al. In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical beta-adrenoceptors in rat colon. Br J Pharmacol. 1990 Aug;100(4):831-9.
[2]. Simiand J, et al. Antidepressant profile in rodents of SR 58611A, a new selective agonist for atypical beta-adrenoceptors. Eur J Pharmacol. 1992 Aug 25;219(2):193-201.
[3]. Claustre Y, et al. Effects of the beta3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: relevance to its antidepressant/anxiolytic-like profile. Neuroscience. 2008 Oct 2;156(2):353-64.