SB-269970 HCl is a HCl salt form of SB-269970, which is a 5-HT7 receptor antagonist with pKi of 8.3 and exhibits > 50-fold selectivity against other receptors.
SB269970 hydrochloride (SB-269970A) is a hydrochloride salt form of SB-269970, which is a 5-HT7 receptor antagonist with the pKi of 8.3, exhibits >50-fold selectivity against other receptors. The pA2 (8.5 ± 0.2) for SB-269970-A agreed well with the pKi determined from [(3)H]-5-CT binding studies. 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes (pEC50 of 8.4 ± 0.2) was inhibited by SB-269970-A (0.3 μM) with a pKB (8.3 ± 0.1) in good agreement with its antagonist potency at the human cloned 5-HT7a receptor and its binding affinity at guinea-pig cortical membranes. 5-CT (0.3 mg/kg, i.p.) induced hypothermia in guinea-pigs was blocked by SB-269970-A (ED50 = 2.96 mg/kg, i.p.) and the non-selective 5-HT7 receptor antagonist metergoline (0.3 - 3 mg/kg, s.c.). SB-269970-A (30 mg/kg) administered at the start of the sleep period, significantly reduced time spent in Paradoxical Sleep (PS) during the first 3 h of EEG recording in conscious rats[2]. Elevated corticosterone level reduces DRN (dorsal raphe nucleus) 5HT7 receptor reactivity and decreases GABAergic transmission within the DRN (dorsal raphe nucleus), which can be reversed by SB 269970[3]. In the fibrogenic phase, both SB-269970 and terguride reduced the serotonin concentrations in lung homogenates and significantly protected against IPF fibrogenic phase by attenuating collagen deposition and mRNA expression of both transforming growth factor-β1 (TGF-β1), and procollagen type Ӏ (PINP)[4].
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