A 5-HT1D receptor antagonist
BRL-15572 2Hcl is a 5-HT1D receptor antagonist with pKi of 7.9, also shows a considerable affinity at 5-HT1A and 5-HT2B receptors, exhibiting 60-fold selectivity over 5-HT1B receptor. IC50 Value: 7.9(pKi)Target: 5-HT1D Receptorin vitro: BRL-15572 displays high affinity and selectivity for h5-HT1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT1D than 5-HT1B receptors. BRL-15572 binds to h5-HT1B and h5-HT1D receptors with pKB of less than 6 and 7.1, respectively. BRL-15572 stimulates [35S]GTP γ S binding in both cell lines, with potencies that correlated with their receptor binding affinities in both h5-HT1B and h5-HT1D receptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6 and 5-HT7 with pKi of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT1D cell line, both BRL-15572 (1 μM) shifts the 5-HT concentration response curve with pKB of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT1A and 5-HT2B receptors.in vivo: In diabetic pithed rats, administration of the selective 5-HT1D receptor antagonist BRL-15572 (2 mg/kg) does not modify the decreased HR induced by vagal electrical stimulation. The effects of L-694,247 (50 μg/kg), a selective agonist for non-rodent 5-HT1B and 5-HT1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572.
参考文献:
[1]. http://en.wikipedia.org/wiki/BRL-15,572
[2]. Fujii H, Takatori S, Zamami Y, Hashikawa-Hobara N, Miyake N, Tangsucharit P, Mio M, Kawasaki H.Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries.Br J Pha
[3]. González-Hernández A, Manrique-Maldonado G, Lozano-Cuenca J, Mu oz-Islas E, Centurión D, Maassen VanDenBrink A, Villalón CM.The 5-HT(1) receptors inhibiting the rat vasodepressor sensory CGRPergic outflow: further involvement of 5-HT(1F), but not 5-HT(1A)
[4]. Rocha-González HI, Blaisdell-López E, Granados-Soto V, Navarrete A.Antinociceptive effect of 7-hydroxy-3,4-dihydrocadalin isolated from Heterotheca inuloides: role of peripheral 5-HT serotonergic receptors.Eur J Pharmacol. 2010 Dec 15;649(1-3):154-60. Ep
[5]. González-Hernández A, Mu oz-Islas E, Lozano-Cuenca J, Ramírez-Rosas MB, Sánchez-López A, Centurión D, Ramírez-San Juan E, Villalón CM.Activation of 5-HT1B receptors inhibits the vasodepressor sensory CGRPergic outflow in pithed rats.Eur J Pharmacol. 2010
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