SB 243213 dihydrochloride

Differential effects of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethyli ndone (SB 243213) on 5-hydroxytryptamine(2C) receptor-mediated responses.[Pubmed:16807362]

J Pharmacol Exp Ther. 2006 Oct;319(1):260-8.

5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethyli ndone (SB 243213) is a selective, high-affinity 5-hydroxytryptamine (serotonin)(2C) receptor ligand that has been previously characterized as a competitive 5-HT(2C) receptor antagonist that has a long duration of activity in vivo. It is active in two preclinical models of anxiety and has an improved anxiolytic profile compared with benzodiazepines. In this study, we further characterized the pharmacological properties of SB 243213 by measuring its effects on each of multiple responses coupled to the 5-HT(2C) receptor. In Chinese hamster ovary cells, SB 243213 was an inverse agonist for the phospholipase A(2) response, for guanosine 5'-O-(3-[(35)S]thio)triphosphate binding, for reduction of constitutive desensitization, and for enhancement of dopamine release in the rat nucleus accumbens, with relative efficacies of 0.6, 1, 1, and 0.6, respectively. However, for the phospholipase C (PLC) signaling cascade, SB 243213 behaved as an antagonist. Although SB 243213 was previously characterized as a competitive antagonist for the PLC response, the magnitude of the dextral shift of the 5-HT concentration-response curve was time-dependent, and the maximal PLC response to 5-HT was decreased, probably as a result of the slow dissociation rate of SB 243213 (initial dissociation rate was 3.2 times slower than SB206553, a prototypical 5-HT(2C) receptor inverse agonist). Taken together, these data show that the pharmacological characteristics of SB 243213 at the 5-HT(2C) receptor differ depending upon the response measured, and they support the hypothesis that different drugs, acting at the same receptor subtype, can differentially regulate multiple cellular signaling systems.

SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety.[Pubmed:11489455]

Neuropharmacology. 2001 Aug;41(2):186-99.

SB-243213 (5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethyl indoline hydrochloride) is a new, selective 5-hydroxytryptamine (5-HT)2C receptor inverse agonist. SB-243213 has high affinity for the human 5-HT2C receptor (pK(i) 9.37) and greater than a 100-fold selectivity over a wide range of neurotransmitter receptors, enzymes and ion channels. In in vitro functional studies, SB-243213 acted as an inverse agonist at the human 5-HT2C receptor with a pK(b) of 9.8. In in vivo studies, SB-243213 was a potent inhibitor of central 5-HT2C receptor-mediated function in rats, blocking meta-chlorophenylpiperazine-induced hypolocomotion with an ID50 of 1.1 mg/kg p.o. and a long duration of action (>8 h). In rats, SB-243213 exhibited anxiolytic-like activity in both the social interaction and Geller-Seifter conflict tests. Importantly, unlike diazepam, chronic administration of SB-243213 did not result in the development of either tolerance to the anxiolytic-like effects or withdrawal anxiogenesis. Furthermore, in rodents, SB-243213 did not affect seizure threshold, did not increase body weight or induce catalepsy, but attenuated the haloperidol-induced catalepsy. SB-243213 did not affect amphetamine-, MK-801- or phencyclidine-induced hyperactivity. In conclusion, SB-243213 may possess an improved anxiolytic profile compared to benzodiazepines. SB-243213 also modulates dopaminergic transmission, lacks pro-psychotic properties and may have utility in the treatment of schizophrenia and motor disorders.

Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: identification of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent.[Pubmed:10737744]

J Med Chem. 2000 Mar 23;43(6):1123-34.

The evolution, synthesis, and biological activity of a novel series of 5-HT(2C) receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT(2C) affinity and selectivity over 5-HT(2A) receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT(2B) receptor. Compounds from this series are inverse agonists at the human cloned 5-HT(2C) receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

SB 243213 hydrochloride is an orally active, selective and high-affinity 5-hydroxytryptamine (5-HT)2C receptor antagonist with a pKi of 9.37 and a pKb of 9.8 for human 5-HT2C receptor. SB 243213 hydrochloride has improved anxiolytic profile and has the potential for schizophrenia and motor disorders.

SB 243213 dihydrochloride,200940-23-4,Natural Products,5-HT Receptor, buy SB 243213 dihydrochloride , SB 243213 dihydrochloride supplier , purchase SB 243213 dihydrochloride , SB 243213 dihydrochloride cost , SB 243213 dihydrochloride manufacturer , order SB 243213 dihydrochloride , high purity SB 243213 dihydrochloride