Uses
BRL-53443 is a potent 5-HT and dopamine receptor agonist. Neuroresearch product.
Definition
ChEBI: 3-(1-methyl-4-piperidinyl)-1H-indol-5-ol is a member of hydroxyindoles.
Biological Activity
A potent 5-ht 1E/1F receptor agonist (pEC 50 values are 8.5 and 8.6 respectively). Displays > 30-fold selectivity over other 5-HT and dopamine receptors (pK i values are 8.7. 8.9, 7.2, 6.9, 7.2, 5.9, 7.0, 6.5, < 6, < 6, 6.3 and 6.2 for human 5-HT 1E , 1F , 1A , 1B , 1D , 2A , 2B , 2C , 4 , 7 , D 2 and D 3 receptors respectively). Induces 5-HT 2A receptor-mediated mouse aortic contraction in vitro (pEC 50 = 6.52). Active in vivo .
in vivo
Reduction of flinching was considered as antinociception. Ipsilateral, but not contralateral, peripheral administration of BRL54443 (5-HT(1E/1F); 3-300 microg/paw) significantly reduced formalin-induced flinching in rats[3].
IC 50
5-HT1E Receptor: 1.1 nM (Ki); 5-HT1F Receptor: 0.7 nM (Ki); 5-HT1A Receptor: 63 nM (Ki); 5-HT1B Receptor: 126 nM (Ki); 5-HT1D Receptor: 63 nM (Ki); 5-HT2A Receptor: 1259 nM (Ki); 5-HT2B Receptor: 100 nM (Ki); 5-HT2C Receptor: 316 nM (Ki); 5-HT6 Receptor: >10,000 nM (Ki); 5-HT7 Receptor: >10,000 nM (Ki)
References
1. a.m. brown, k. avenell, t j. young et al. brl 54443, a potent agonist with selectivity for human cloned 5-ht1e and 5-ht1f receptors. 1998. br.j.pharmacol. 123 233p.2. s. lightowler, t. stean, n. upton et al. effect of brl 54443 (3-(1-methylpiperidin-4-yl)-1h-indol-5-ol), a 5-ht1e/1f receptor agonist, on general behaviour and maximal electroshock seizure threshold in the rat. 1998. br.j.pharmacol. 123 237p.3. mckune cm, watts sw. characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling. j pharmacol exp ther. 2001 apr;297(1):88-95.4. janssen p, tack j, sifrim d et al. influence of 5-ht1 receptor agonists on feline stomach relaxation. eur j pharmacol. 2004 may 25;492(2-3):259-67.
