Biochemical and behavioral studies of the 5‐HT1B receptor agonist, CP‐94,253

  title={Biochemical and behavioral studies of the 5‐HT1B receptor agonist, CP‐94,253},
  author={Billie Kenneth Koe and Jann A. Nielsen and John Eugene Macor and James Heym},
  journal={Drug Development Research},
CP‐94,253, 3‐(1,2,5,6‐tetrahydro‐4‐pyridyl)‐5‐propoxypyrrolo[3,2‐b]pyridine, a new serotonergic ligand, was found to exhibit significantly greater binding affinity at 5‐HT1B receptors than at 5‐HT1A or 5‐HT1C receptors. Saturation studies showed CP‐94,253 to be a competitive inhibitor of [125l]iodocyanopindolol binding to 5‐HT1B sites. Its competition curve with this radioligand was shifted to the right (decreased affinity) in the presence of Gpp(NH)p, indicating an agonist function for CP‐94… 

The anxiolytic‐like effect of 5‐HT1B receptor ligands in rats: a possible mechanism of action

The results suggested that the anxiolytic‐like effect of the 5‐HT1B receptor ligands CP 94253, SB 216641 and GR 127935 was possibly linked to the postsynaptic 5‐ht1B receptors or/and 5‐ HT1B heteroreceptors.

Dopamine uptake inhibitory activity of novel tryptamine 5‐HT1 receptor ligands

The potent effect of these 5‐HT1 receptor ligands on dopamine uptake can be rationalized by the observation that the flexibility of these tryptamine molecules allows the superimposition of the phenyl ring and amino group of the side chain with the corresponding moieties of tametraline, a known catecholamine uptake inhibitor of fixed conformation.

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

The results imply that CP-94,253 probes a role for central 5- HT1B 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.

The role of 5‐HT1B receptors in the regulation of serotonin cell firing and release in the rat brain

5‐HT cell firing and release in midbrain raphe nuclei (particularly in the MnR) are under control of 5‐HT1B receptors, and the effects of higher concentrations of5‐ HT1B receptor agonists seem more compatible with the activation of 5-HT1b heteroreceptors on inhibitory neurons.

Evidence that 5‐hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5‐HT1A, 5‐HT1B and 5‐HT1D autoreceptors

The results suggest that 5‐HT release in the rat DRN is under the control of 5‐ HT1A,5‐HT1B and 5-HT1D autoreceptors.

Tonic regulation of satiety by 5‐HT1B receptors in the mouse: converging evidence from behavioural and c‐fos immunoreactivity studies?

The results suggest that the activation of 5‐HT1B receptors is an important component of endogenous satiation mechanisms in the mouse.

Functional characterization of 5‐HT1D autoreceptors on the modulation of 5‐HT release in guinea‐pig mesencephalic raphe, hippocampus and frontal cortex

The results confirm the presence of functional 5‐ HT1D autoreceptors controlling 5‐HT release within the mesencephalic raphe as well as in terminal regions and suggest that, in addition to the 5-HT1D Autoreceptor activated by sumatriptan, another subtype of 5‐ht autoreceptor is activated by 5‐MeOT in the hippocampus.

5‐HT1A and 5‐HT1B receptors control the firing of serotoninergic neurons in the dorsal raphe nucleus of the mouse: studies in 5‐HT1B knock‐out mice

Data indicate that in the mouse, the firing of 5‐HT neurons in the dorsal raphe nucleus is under both an inhibitory control through 4‐methyl‐piperazine‐1‐yl and an excitatory influence through5‐HT1B receptors.

CP-135,807, a selective 5-HT1D agonist: effects in drug discrimination and punishment procedures in the pigeon

Results suggest that CP-135,807 produces centrally mediated psychoactive effects that differ distinctly from those of 5-HT1A agonists.



Characterization of [3H]CP‐96,501 as a Selective Radioligand for the Serotonin 5‐HT1B Receptor: Binding Studies in Rat Brain Membranes

The results of this study suggest that [3H]CP‐96,501 is a useful agonist radioligand for the 5‐HT1B receptor.

Binding and uptake studies with [3H]CP‐93, 129, a radiolabeled selective 5‐HT1B receptor ligand

High affinity binding sites of CP‐93, 129 were found in rat whole brain membranes, which showed KD and Bmax values similar to those for 5‐HT1B sites labeled by [3H]5‐HT.

Pharmacological Differentiation and Characterization of 5‐HT1A, 5‐HT1B, and 5‐HT1C Binding Sites in Rat Frontal Cortex

  • S. Peroutka
  • Biology, Chemistry
    Journal of neurochemistry
  • 1986
Computer‐assisted iterative curve fitting suggests that these drugs can discriminate two distinct subpopulations of non‐5‐ HT1A binding sites, each representing ∼35% of the total [3H]5‐HT binding in the rat frontal cortex.

5-HT1B agonists induce anorexia at a postsynaptic site.

Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes

  • R. E. HeuringS. Peroutka
  • Biology, Chemistry
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1987
The data demonstrate the presence of a homogeneous class of 5- HT1 binding sites in bovine caudate that is pharmacologically distinct from previously defined 5-HT1A, 5-ht1B, 5 - HT1C, 4-HT2, 3-HT3 receptor subtypes.

3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1B) agonist and rotationally restricted phenolic analogue of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole.

2 appears to lie in the ability of a pyrrolo[3,2-b]pyrid-5-one to act as a rotationally restricted bioisosteric replacement for 5-hydroxyindole, which is shown to be biochemically discriminatory in its ability to selectively inhibit forskolin-stimulated adenylate cyclase activity only at the 5-HT1B receptor.

5-HT receptor subtypes outside the central nervous system. Roles in the physiology of the gut.

It is proposed that 5- HT1P receptors and perhaps 5-HT3 receptors are involved in initiating the peristaltic reflex and in regulating gastric emptying in the enteric nervous system.