RTI-13951-33是一种有效、选择性、可透过血脑屏障的GPR88激动剂，在GPR88cAMP功能性实验中，EC50值为25nM。RTI-13951-33可以减少大鼠酒精强化和摄取行为。
RTI-13951-33 is a potent, selective, and brain-penetrant GPR88 agonist, with an EC50 of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 reduces alcohol reinforcement and intake behaviors in rats[1].
RTI-13951-33 is a potent, selective, and brain-penetrant GPR88 agonist, with an EC50 of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 elevates [35S]-GTPγS binding (EC50， 535 nM) in mouse striatal membranes but not in membranes from GPR88 KO mice[1].RTI-13951-33 has weak affinities at kappa opioid receptor (KOR; Ki, 2.29 μM), vesicular monoamine transporter (VMAT; Ki, 4.23 μM), and moderate affinity at serotonin transporter (SERT; Ki, 0.75 μM), however, RTI-13951-33 poorly inhibits SERT (IC50, 25.1 ± 2.7 μM)[1].
RTI-13951-33 (10 mg/kg, i.p.) has sufficient brain penetration, with t1/2 of 48 min and 87 min in rat plasma and brain[1].RTI-13951-33 (10 and 20 mg/kg, i.p.) dose-dependently decreases alcohol lever responses in a rat model of alcohol self-administration[1].
[1]. Jin C, et al. Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake. J Med Chem. 2018 Aug 9;61(15):6748-6758.
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