SR 58611A hydrochloride

The beta3 adrenoceptor agonist, amibegron (SR58611A) counteracts stress-induced behavioral and neurochemical changes.[Pubmed:20537869]

Eur Neuropsychopharmacol. 2010 Oct;20(10):704-13.

These experiments were made to study the mechanisms underlying the antidepressant-like effects of the beta(3) adrenoceptor agonist amibegron (SR58611A). To this purpose, the expression levels of the hippocampal cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), B-cell lymphoma-2 (Bcl-2) and Bax proteins were assessed, by using western blot analysis, in rats tested in the forced swim test (FST). Under basal conditions (no previous exposure to stressors), different groups of male Wistar rats received acutely or repeatedly (once/day for 7days) intraperitoneal (i.p.) injections of amibegron (1, 5 and 10mg/kg), the tricyclic antidepressant (TCA) clomipramine (50mg/kg), the selective serotonin reuptake inhibitor (SSRI) citalopram (15mg/kg) or their vehicles. The influence of stress-related conditions was studied in rats subjected to acute (4h) or repeated (4h/day for 7days) restraint stress, applied prior to the FST procedure. Compared to the control groups, both stressor procedures increased the immobility time in the FST and reduced hippocampal BDNF and Bcl-2/Bax ratio proteins expression, which were counteracted by amibegron (5 and 10mg/kg) treatment. Opposite effects were found in the CREB expression, since it was lower after acute and higher after repeated stress procedure, respectively. Again, these effects were reversed by amibegron treatment. Different results were obtained in animals treated with clomipramine or citalopram. Hence, it is likely that the observed behavioral effects of amibegron could be due, at least in part, to its action on hippocampal expression of neurotrophic and/or anti-apoptotic factors, supporting the hypothesis that beta(3) adrenoceptors may be a therapeutic target for the treatment of stress-related disorders.

Effects of the beta3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: relevance to its antidepressant/anxiolytic-like profile.[Pubmed:18691638]

Neuroscience. 2008 Oct 2;156(2):353-64.

SR58611A is a selective beta(3)-adrenoceptor (Adrb3) agonist which has demonstrated antidepressant and anxiolytic properties in rodents. The present study confirmed the detection of Adrb3 mRNA transcript in rodent brain sub-regions and evaluated the effect of SR58611A on serotonergic and noradrenergic transmission in rats and mice in an attempt to elucidate the mechanism(s) underlying these properties. SR58611A (3 and 10 mg/kg, p.o.) increased the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas (cortex, hippocampus, hypothalamus, striatum). Moreover, SR58611A (10 mg/kg, p.o.) increased the release of 5-HT assessed by in vivo microdialysis in rat prefrontal cortex. Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.), in contrast to fluoxetine (15 mg/kg, p.o.), did not modify the activity of serotonergic neurons in the rat dorsal raphe nucleus. The increase in 5-HT synthesis induced by SR58611A was not observed in Adrb3s knockout mice, suggesting a selective involvement of Adrb3s in this effect. SR58611A (3 and 10 mg/kg, p.o.) did not modify norepinephrine synthesis and metabolism but increased its release in rat brain. Repeated administration of SR58611A (10 mg/kg, p.o.) did not modify basal norepinephrine release in rat prefrontal cortex whereas it prevented its tail-pinch stress-induced enhancement similarly to reboxetine (15 mg/kg, p.o.). Finally SR58611A increased the firing rate of noradrenergic neurons in the rat locus coeruleus following systemic (3 mg/kg, i.v.) or local (0.01 and 1 microM) but not chronic (10 mg/kg, p.o.) administration. These results suggest that the anxiolytic- and antidepressant-like activities of SR58611A involve an increase of brain serotonergic and noradrenergic neurotransmissions, triggered by activation of Adrb3s.

Stimulation of the beta3-Adrenoceptor as a novel treatment strategy for anxiety and depressive disorders.[Pubmed:17460614]

Neuropsychopharmacology. 2008 Feb;33(3):574-87.

The characterization of the first selective orally active and brain-penetrant beta3-adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stress-induced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the beta3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide. Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the beta3 adrenoceptor suggested that these effects of SR58611A are mediated by beta3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of beta3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.

Behavioral effects of the beta3 adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant/anxiolytic drugs?[Pubmed:17669397]

Eur J Pharmacol. 2007 Nov 14;573(1-3):139-47.

A large body of evidence corroborates the notion that deficiencies of serotonergic system are likely involved in the pathogenesis of both depression and anxiety. Activation of beta(3) adrenoceptors has been shown to increase brain tryptophan content suggesting an elevation of brain serotonin (5HT) synthesis. SR58611A is a selective beta(3) adrenergic agent possessing a profile of antidepressant activity in routine rodents' experimental models of depression. The present study was undertaken to evaluate in rodents the antidepressant properties of SR58611A and to assess its putative anxiolytic value in experimental models of depression and anxiety. Compared to the control group, SR58611A (0.1, 1, 5 or 10 mg/kg) caused a dose-dependent reduction in immobility of Wistar male rats in the forced swim test. The maximum dose appeared to be equivalent to an effective dose of clomipramine (50 mg/kg). In addition, acute injection of SR58611A induced in rats a dose-dependent decrease in grooming response to a novel environment (novelty-induced grooming test). For any dose, the effect was lower than that of diazepam (1 mg/kg). Chronic treatment with SR58611A resulted also in an increased social interaction time in the social interaction test without affecting motor activity of rats. Furthermore, similarly to diazepam a chronic treatment with the highest doses of SR58611A was followed by increased exploratory behavior in Swiss male mice exposed to the elevated plus maze test. These effects are mediated by beta(3) adrenoceptors since i.p. pretreatment with the selective beta(3) adrenoceptor antagonist SR59230A (5 mg/kg) blocked the effects of SR58611A. Finally, also the 5HT antagonist methysergide (2 mg/kg) prevented the antidepressant and anxiolytic-like activity of SR58611A indicating that 5HT transmission is strictly involved in its action.

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.

SR 58611A hydrochloride,121524-09-2,Natural Products,Adrenergic Receptor, buy SR 58611A hydrochloride , SR 58611A hydrochloride supplier , purchase SR 58611A hydrochloride , SR 58611A hydrochloride cost , SR 58611A hydrochloride manufacturer , order SR 58611A hydrochloride , high purity SR 58611A hydrochloride