Summary
The in vitro and in vivo characteristics of CP-93,129 [Structure 1 in Figure 1, 3-(1,2,5,6-tetrahydropyrid-4-yl)-pyrrolo[3,2-b]pyrid-5-one] are described. This rotationally restricted phenolic analog of RU-24,969 is a potent (15 nm) and selective (200 × vs. the 5-HT1A receptor, 150 × vs. the 5-HT1D receptor) functional agonist for the 5-HT1B receptor. Direct infusion of CP-93, I29 into the paraventricular nucleus of the hypothalamus of rats significantly inhibits food intake, implicating the role of 5-HT1B receptors in regularing feeding behavior in rodents. CP-93,129 has also been shown to be biochemically discriminatory in its ability to selectively inhibit forskolin-stimulated adenylate cyclase activity only at the 5-HT1B receptor. The source of the selectivity of CP-93,129 appears to lie in the ability of a pyrrolo[3,2-b]pyrid5-one to act as a rotationally restricted bioisosteric replacement for 5-hydroxyindole.
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Macor, J.E. et al. (1991). CP-93,129: A Potent and Selective Agonist for the Serotonin (5-HT1B) Receptor and Rotationally Restricted Analog of RU-24,969. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_45
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DOI: https://doi.org/10.1007/978-3-0348-7259-1_45
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