CP-94,253: a selective serotonin1B (5-HT1B) agonist that promotes satiety

Abstract

The selective 5-HT_1B agonist CP-94,253 (3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b] pyridine) (5–40 μmol/kg) reduced the intake of both pellets and a 10% solution of sucrose (ID₅₀ = 12.5 and 22.8 μmol/kg, respectively) in mildly deprived rats. Time-sampled observations revealed that CP-94,253 terminated feeding earlier, without disrupting the continuity of feeding. CP-94,253 increased standing but did not promote resting during satiation. Microstructural analysis of licking indicated that CP-94,253 decreased the frequency, but not the size, of bursts and clusters of licks without altering oral motor efficiency. The peripherally acting 5-HT_1B agonist, CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one) had no effect on food intake. These results imply that CP-94,253 probes a role for central 5-HT_1B receptors in the regulation of meal size and duration, but that recruitment of other 5-HT receptor subtypes may be needed for the full expression of satiety.