PubMed Health⌕ Search

PubMed · 14584972

SR 58611A: SR 58611.

Abstract

SR 58611A [SR 58611], a highly selective agonist for atypical beta3-adrenoceptors, inhibits intestinal motility. This (phenylethanol) aminotetraline sympathomimetic was originated by Sanofi as a potential treatment for irritable bowel syndrome but is now in development for depression. SR 58611A is currently in phase III trials for depression in France. A phase IIa trial of SR 58611A in patients with severe recurrent depression showed it to be superior to fluoxetine and well tolerated, while a phase IIb trial demonstrated comparable efficacy and tolerability to paroxetine. SR 58611A was in phase II clinical trials in France for irritable bowel syndrome but there is no record of active development of SR 58611A for this indication. SR 58611A had also been in phase IIa for the treatment of obesity but no recent development has been reported for this indication. SR 58878 is the acid metabolite of SR 58611A.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

2003. SR 58611A: SR 58611.. https://doi.org/10.2165/00126839-200304060-00012

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Potent benzimidazolone based human beta(3)-adrenergic receptor agonists.

The synthesis and biological evaluation of a series of benzimidazolone beta(3) adrenergic receptor agonists are described. A trend toward the reduction of rat atrial tachycardia upon increasing steric bulk at the 3-position of the benzimidazolone moiety was observed.

Adrenergic beta-3 Receptor Antagonists↗

Pharmacological evidence for beta3 adrenoceptors in the control of rat gastric acid secretion.

The effect of the beta3-adrenoceptor agonist BRL37344 on gastric acid secretion evoked by different secretory stimuli was investigated in anaesthetized rats with lumen-perfused stomachs in comparison with the beta2-adrenoceptor agonist clenbuterol. Intravenous injections of BRL37344 (1-10 micromol/kg) and clenbuterol (0.01-1 micromol/kg) dose-dependently reduced 2-deoxy-D-glucose-induced acid secretion, with BRL37344 about forty times less potent than clenbuterol. BRL37344 (0.1-3 micromol/kg) inhibited pentagastrin-induced acid output, whereas clenbuterol was effective only at high doses (10-100 micromol/kg). The inhibitory effect of BRL37344 on pentagastrin-induced acid secretion was not modified by the nonselective beta-adrenoceptor antagonist propranolol, but it was prevented by bupranolol, a beta3-adrenoceptor antagonist. Furthermore, neither BRL37344 (10 micromol/kg) nor clenbuterol (100 micromol/kg) modified the acid secretion induced by histamine. These data suggest that beta3 adrenoceptors have an inhibitory role in the control of rat gastric acid secretion induced by indirect stimuli.

Adrenergic beta-3 Receptor Antagonists↗

Beta3 adrenergic stimulation inhibits the opossum lower esophageal sphincter.

BACKGROUND & AIMS: Previous studies have identified adrenergic receptor sites in the lower esophageal sphincter (LES) of animals and humans. A beta3 adrenoceptor has been identified and cloned. The binding site for this receptor has been found in the rat LES in vitro. The aim of the study was to assess the role of a specific beta3 agonist (CL316243) on LES pressure (LESP) in vivo. METHODS: Anesthetized adult opossums were given CL316243 and isoproterenol intravenously as boluses before and after continuous infusion of L748337 (a specific beta3 antagonist), propranolol, and bethanechol. Blood pressure, heart rate, and LESP were continuously recorded. RESULTS: CL316243 caused a dose-dependent maximal inhibition of LESP of 88.5% +/- 4.8%. The mean duration of inhibition was 62.2 +/- 9.2 minutes with minimal change in cardiovascular parameters. Isoproterenol caused dose-dependent maximal inhibition of 89.4% +/- 4.7% with mean duration of action of 5.1 +/- 0.9 minutes but was associated with significant hypotension and tachycardia. L748337 and propranolol significantly blocked the effects of CL316243 and isoproterenol, respectively. CL316243 and isoproterenol inhibited the bethanechol-mediated hypertensive LES. CONCLUSIONS: (1) A selective beta3 agonist, CL316243, caused significant, prolonged, and dose-dependent inhibition of LESP and, unlike isoproterenol, had minimal effect on heart rate and mean arterial pressure. (2) The beta3 antagonist, L748337, selectively inhibited CL316243 without altering the isoproterenol response. (3) CL316243 and isoproterenol both caused inhibition of cholinergic-mediated hypertensive LESP.

Adrenergic beta-3 Receptor Antagonists↗