A 5-HT7 receptor agonist
AS 19 is a potential 5-HT7 receptor agonist with an IC50 value of 0.83 nM [1].
5-HT7 receptor plays a role in the control of both sleep and circadian rhythms. This receptor may also play a role in other CNS disorders including cognitive disturbances, anxiety and migraine probably via both central and peripheral mechanisms [2].
By signaling through the 5-HT7 receptor, serotonin provides an accessory signal to enhance the activation of the T-cell. Compared with saline-treated controls, the proliferation of T-cell from PCPA-treated mice was significantly reduced. The PCPA inhibition efficacy ranged from approximately 18% to 49%. Addition of exogenous 5-HT at 1 μM completely restored the proliferation of the T-cell. Similar to exogenous 5-HT, addition of AS19 at 1 μM also completely restored T-cell proliferation after 48 hours [4].
SB-258719 is a selective 5-HT7 receptor antagonist. When AS-19 at a dose of 10 mg/kg was co-administered with SB-258719 at the same dose, which produced no effect on its own, the anti-hyperalgesic effect of AS-19 was reversed in both hotplate and tail-flick tests. That meant AS-19 exerts anti-hyperalgesic effect via 5-HT7 receptors [3]. SB269970 is also a selective 5-HT7 receptor antagonist. Some rats were prepared with a second intrathecal catheter and were pretreated with 7μl SB269970 at a concentration of 5mM. At all time points, AS-19-induced PMF was abolished by SB269970 pretreatment. This meant AS-19 elicited PMF via the activation of 5-HT7 receptor [5].
参考文献:
[1].? Perez-García GS and Meneses A. Effects of the potential 5-HT7 receptor agonist AS 19 in an autoshaping learning task. Behav Brain Res, 2005, 163(1):136-40.
[2].? Thomas DR and Hagan JJ. 5-HT7 Receptors. Current Drug Targets-CNS & Neurological Disorders, 2004, 3(1): 81-90.
[3].? Ulugol A, Oltulu C, Gunduz O, et al. 5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice. Pharmacol Biochem Behav, 2012, 102(2):344-8.
[4].? León-Ponte M, Ahern GP and O'Connell PJ. Serotonin provides an accessory signal to enhance T-cell activation by signaling through the 5-HT7 receptor. Blood, 2007, 109(8):3139-46.
[5].? Hoffman MS and Mitchell GS. Spinal 5-HT7 receptor activation induces long-lasting phrenic motor facilitation. J Physiol, 2011, 589(Pt 6):1397-407.
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