SB 243213
目录号 : GC61268
A 5-HT2C receptor inverse agonist
Cas No.:200940-22-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SB-243213 is an inverse agonist of the serotonin (5-HT) receptor subtype 5-HT2C.1 It is selective for 5-HT2C over 5-HT2A and 5-HT2B receptors (Kis = 0.001, 0.158, and 0.1 ?M, respectively) and the cytochrome P450 (CYP) isoforms CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (IC50s = >100, 23, >100, >100, and >100 ?M, respectively). SB-243213 reduces the basal activity of 5-HT2C in HEK293 cells expressing the human 5-HT2C receptor (pKB = 9.5). It reverses mCPP-induced hypolocomotion in rats (ID50 = 0.7 mg/kg). SB-243213 (0.2-5 mg/kg) has anxiolytic-like activity in the social interaction test in rats.
1.Bromidge, S.M., Dabbs, S., Davies, D.T., et al.Biarylcarbamoylindolines are novel and selective 5-HT2C 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 agentJ. Med. Chem.43(6)1123-1134(2000)
| Cas No. | 200940-22-3 | SDF | |
| Canonical SMILES | O=C(N1CCC2=C1C=C(C(F)(F)F)C(C)=C2)NC3=CC=C(OC4=CC=CN=C4C)N=C3 | ||
| 分子式 | C22H19F3N4O2 | 分子量 | 428.41 |
| 溶解度 | DMSO : 125 mg/mL (291.78 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3342 mL | 11.6711 mL | 23.3421 mL |
| 5 mM | 0.4668 mL | 2.3342 mL | 4.6684 mL |
| 10 mM | 0.2334 mL | 1.1671 mL | 2.3342 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Differential effects of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethylindone (SB 243213) on 5-hydroxytryptamine(2C) receptor-mediated responses
J Pharmacol Exp Ther 2006 Oct;319(1):260-8.PMID:16807362DOI:10.1124/jpet.106.104448.
5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethylindone (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.
Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors
Psychopharmacology (Berl) 2009 Nov;207(1):119-25.PMID:19688201DOI:10.1007/s00213-009-1639-8.
Introduction: Substantial increases in body weight can be induced by several antipsychotic drugs, most notably olanzapine and clozapine. Antagonism at certain receptors, particularly 5-HT2C and histamine H1 receptors, is implicated in this effect. Materials and methods: We have investigated the contribution of effects at these receptors to olanzapine-induced weight gain occurring over 5 days following daily intraperitoneal drug injections in groups of eight female rats. Results: Olanzapine (2 mg/kg) and the 5-HT2C antagonist SB 243213 (1 mg/kg), but not the histamine H1 antagonist mepyramine (1 mg/kg), produced significant increases in percentage body weight above vehicle; olanzapine showed a significantly greater effect than SB 243213. Haloperidol (0.1 mg/kg) alone or with mepyramine had no significant effects on weight gain, while with SB 243213 and with both SB 243213 and mepyramine, it showed olanzapine-like increases in weight. Conclusion: These results suggest that 5-HT2C receptor antagonism or inverse agonism, in the presence of D2 receptor antagonism, may contribute to olanzapine-induced weight gain.
Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo
Biol Psychiatry 2006 Mar 15;59(6):568-75.PMID:16182256DOI:10.1016/j.biopsych.2005.07.035.
Background: Central serotonin2C (5-HT2C) receptors are known to play a role in the mechanism of action of the antipsychotic drugs (APDs) clozapine and haloperidol. However, evidence for the involvement of the constitutive activity of 5-HT2C receptors in the dopamine (DA)ergic effects of APDs is lacking in vivo. Methods: Using in vivo microdialysis in halothane-anesthetized rats, we assessed the ability of selective 5-HT2C compounds to modulate the release of DA induced by haloperidol and clozapine in the nucleus accumbens and striatum. Results: Both APDs induced a dose-dependent increase in accumbal and striatal DA extracellular levels. The effect of .01 mg/kg haloperidol was potentiated by the 5-HT2C inverse agonist SB 206553 (5 mg/kg) but unaltered by the 5-HT2C antagonists SB 243213 and SB 242084 (1 mg/kg). Conversely, the effect of 1 mg/kg clozapine, a dose able to reverse the decrease in DA outflow induced by the 5-HT2C agonist Ro 60-0175 (3 mg/kg), was unaffected by SB 206553 but blocked by SB 243213 (1 mg/kg) and SB 242084 (.3 and 1 mg/kg). Conclusions: These results show that clozapine and haloperidol differentially alter the constitutive activity of 5-HT2C receptors and suggest that clozapine behaves as a 5-HT2C inverse agonist in vivo.
Diverse effects of 5-HT2C receptor blocking agents on c-Fos expression in the rat basal ganglia
Eur J Pharmacol 2012 Aug 15;689(1-3):8-16.PMID:22643326DOI:10.1016/j.ejphar.2012.05.022.
Serotonin(2C) receptors (5-HT(2)C) exert continuous control on the activity of specific populations of neurons in the basal ganglia. While antagonists block the effect of endogenous 5-HT at 5-HT(2C) receptors, the actions of inverse agonists may also involve interruption of activity at constitutively active populations of 5-HT(2C) receptors. We have evaluated the regional impact of these controls by studying, in rats, the expression of the product of the proto-oncogene c-Fos in rat basal ganglia after peripheral doses of the 5-HT(2C) antagonist SB 243213 (5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline) and the 5-HT(2B/2C) inverse agonists SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole.hydrochloride) and S32006 (N-pyridin-3-yl-1,2-dihydro-3H-benzo[e]indole-3-carboxamide). The results show that 1 and 10mg/kg SB 243213 enhanced equally c-Fos expression in the subthalamic nucleus (STN) and dose-dependently in the striatum and nucleus accumbens core (NAcc). SB 206553 (1-10mg/kg), at 10mg/kg only, enhanced c-Fos expression in STN, striatum (except the dorsomedial part), NAcc, entopeduncular nucleus, substantia nigra pars reticulata (SNr) and compacta (SNc) and ventral tegmental area. S32006 induced a similar increase in c-Fos expression in the medial parts of the striatum and NAcc at doses of 1-10mg/kg while it dose-dependently enhanced c-Fos expression in medial parts of the STN and SNr. None of these drugs induced c-Fos expression in the globus pallidus. The distinct pattern of c-Fos expression elicited by the 5-HT(2C) antagonist and inverse agonists suggests the existence of cellular and functional heterogeneity in the response of the basal ganglia to drugs inhibiting 5-HT(2C) receptors.
A Subset of Purposeless Oral Movements Triggered by Dopaminergic Agonists Is Modulated by 5-HT2C Receptors in Rats: Implication of the Subthalamic Nucleus
Int J Mol Sci 2020 Nov 12;21(22):8509.PMID:33198169DOI:10.3390/ijms21228509.
Dopaminergic medication for Parkinson's disease is associated with troubling dystonia and dyskinesia and, in rodents, dopaminergic agonists likewise induce a variety of orofacial motor responses, certain of which are mimicked by serotonin2C (5-HT2C) receptor agonists. However, the neural substrates underlying these communalities and their interrelationship remain unclear. In Sprague-Dawley rats, the dopaminergic agonist, apomorphine (0.03-0.3 mg/kg) and the preferential D2/3 receptor agonist quinpirole (0.2-0.5 mg/kg), induced purposeless oral movements (chewing, jaw tremor, tongue darting). The 5-HT2C receptor antagonist 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethylindone (SB 243213) (1 mg/kg) reduced the oral responses elicited by specific doses of both agonists (0.1 mg/kg apomorphine; 0.5 mg/kg quinpirole). After having confirmed that the oral bouts induced by quinpirole 0.5 mg/kg were blocked by another 5-HT2C antagonist (6-chloro-5-methyl-1-[6-(2-methylpiridin-3-yloxy)pyridine-3-yl carbamoyl] indoline (SB 242084), 1 mg/kg), we mapped the changes in neuronal activity in numerous sub-territories of the basal ganglia using c-Fos expression. We found a marked increase of c-Fos expression in the subthalamic nucleus (STN) in combining quinpirole (0.5 mg/kg) with either SB 243213 or SB 242084. In a parallel set of electrophysiological experiments, the same combination of SB 243213/quinpirole produced an irregular pattern of discharge and an increase in the firing rate of STN neurons. Finally, it was shown that upon the electrical stimulation of the anterior cingulate cortex, quinpirole (0.5 mg/kg) increased the response of substantia nigra pars reticulata neurons corresponding to activation of the "hyperdirect" (cortico-subthalamonigral) pathway. This effect of quinpirole was abolished by the two 5-HT2C antagonists. Collectively, these results suggest that induction of orofacial motor responses by D2/3 receptor stimulation involves 5-HT2C receptor-mediated activation of the STN by recruitment of the hyperdirect (cortico-subthalamonigral) pathway.