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

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.

Effects of the vasopressin (V1b) receptor antagonist, SSR149415, and the corticotropin-releasing factor 1 receptor antagonist, SSR125543, on FG 7142-induced increase in acetylcholine and norepinephrine release in the rat.

Arginine vasopressin and corticotropin-releasing factor are two neuroactive peptides that regulate hypothalamic-pituitary-axis and associated stress response. While the potential antidepressant and anxiolytic profiles of corticotropin-releasing factor 1 antagonists have been well studied, the concept of blockade of vasopressin system as another approach for the treatment of emotional processes has only been made available recently by the synthesis of the first non-peptide antagonist at the V1b receptor, SSR149415. In the present study SSR149415 has been compared with the corticotropin-releasing factor 1 antagonist SSR125543 and with anxiolytic and antidepressant drugs on the response of hippocampal cholinergic and cortical noradrenergic systems to the anxiogenic benzodiazepine receptor inverse agonist FG 7142.

SSR181507, a dopamine D(2) receptor antagonist and 5-HT(1A) receptor agonist. I: Neurochemical and electrophysiological profile.

SSR181507 ((3-exo)-8-benzoyl-N-[[(2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.1]octane-3-methanamine monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT(1A) receptors (K(I)=0.

SSR180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide), a peripheral benzodiazepine receptor ligand, promotes neuronal survival and repair.

In the present study, we have investigated the potential neuroprotective effects of a novel peripheral benzodiazepine binding site (PBR) ligand, 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide (SSR180575), in models of central and peripheral neurodegeneration in vivo and its effect on steroid concentrations in plasma and nervous tissue. SSR180575 shows high affinity (IC(50), 2.5-3.

The preclinical pharmacologic profile of tiapride.

Tiapride is a benzamide derivative that has been used successfully in the clinic for a number of years for the treatment of agitation and aggressiveness in elderly patients. Like many substituted benzamides, tiapride specifically blocks dopamine receptors in the brain. It has affinity for dopamine D(2) (IC(50) = 110-320 nM) and D(3) (IC(50) = 180 nM) receptors in vitro but lacks affinity for dopamine D(1) and D(4) receptors and for non-dopaminergic receptors including H(1), alpha(1), alpha(2)-adrenergic and serotonergic receptors.