For research use only. Not for therapeutic Use.
SB 272183 is a highly potent dual 5-HT1A and 5-HT1B antagonists as potential antidepressant drug.
| Catalog Number | I009329 |
| CAS Number | 216058-27-4 |
| Synonyms | SB 272183; SB272183; SB-272183.;5-chloro-6-(4-methylpiperazin-1-yl)-N-(4-pyridin-4-ylnaphthalen-1-yl)-2,3-dihydroindole-1-carboxamide |
| Molecular Formula | C29H28ClN5O |
| Purity | ≥95% |
| Solubility | Soluble in DMSO |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| InChI | InChI=1S/C29H28ClN5O/c1-33-14-16-34(17-15-33)28-19-27-21(18-25(28)30)10-13-35(27)29(36)32-26-7-6-22(20-8-11-31-12-9-20)23-4-2-3-5-24(23)26/h2-9,11-12,18-19H,10,13-17H2,1H3,(H,32,36) |
| InChIKey | DAPBIPAGJXKFCI-UHFFFAOYSA-N |
| SMILES | O=C(N1CCC2=C1C=C(N3CCN(C)CC3)C(Cl)=C2)NC4=C5C=CC=CC5=C(C6=CC=NC=C6)C=C4 |
| Reference | 1:Br J Pharmacol. 2001 Jul;133(6):797-806. SB-272183, a selective 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptor antagonist in native tissue.Watson J,Roberts C,Scott C,Kendall I,Collin L,Day NC,Harries MH,Soffin E,Davies CH,Randall AD,Heightman T,Gaster L,Wyman P,Parker C,Price GW,Middlemiss DN, PMID: 11454652 PMCID: PMC1572841 DOI: 10.1038/sj.bjp.0704133 </br><span>Abstract:</span> A novel compound, SB-272183 (5-Chloro-2, 3-dihydro-6-[4-methylpiperazin-1-yl]-1[4-pyridin-4-yl]napth-1-ylaminocarbonyl]-1H-indole), has been shown to have high affinity for human 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors with pK(i) values of 8.0, 8.1 and 8.7 respectively and is at least 30 fold selective over a range of other receptors. [(35)S]-GTPgammaS binding studies showed that SB-272183 acts as a partial agonist at human recombinant 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors with intrinsic activities of 0.4, 0.4 and 0.8 respectively, compared to 5-HT. SB-272183 inhibited 5-HT-induced stimulation of [(35)S]-GTPgammaS binding at human 5-HT(1A) and 5-HT(1B) receptors to give pA(2) values of 8.2 and 8.5 respectively. However, from [(35)S]-GTPgammaS autoradiographic studies in rat and human dorsal raphe nucleus, SB-272183 did not display intrinsic activity up to 10 microM but did block 5-HT-induced stimulation of [(35)S]-GTPgammaS binding. From electrophysiological studies in rat raphe slices in vitro, SB-272183 did not effect cell firing rate up to 1 microM but was able to attenuate (+)8-OH-DPAT-induced inhibition of cell firing to give an apparent pK(b) of 7.1. SB-272183 potentiated electrically-stimulated [(3)H]-5-HT release from rat and guinea-pig cortical slices at 100 and 1000 nM, similar to results previously obtained with the 5-HT(1B) and 5-HT(1D) receptor antagonist, GR127935. Fast cyclic voltammetry studies in rat dorsal raphe nucleus showed that SB-272183 could block sumatriptan-induced inhibition of 5-HT efflux, with an apparent pK(b) of 7.2, but did not effect basal efflux up to 1 microM. These studies show that, in vitro, SB-272183 acts as an antagonist at native tissue 5-HT(1A), 5-HT(1B) and 5-HT(1D) receptors. |
