5-HT4 receptor antagonist affinities of SB207710, SB205008, and SB203186 in the human colon, rat oesophagus, and guinea-pig ileum peristaltic reflex

  title={5-HT4 receptor antagonist affinities of SB207710, SB205008, and SB203186 in the human colon, rat oesophagus, and guinea-pig ileum peristaltic reflex},
  author={Peter G. Mclean and Ian M. Coupar},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  • P. Mclean, I. Coupar
  • Published 1 August 1995
  • Chemistry, Medicine
  • Naunyn-Schmiedeberg's Archives of Pharmacology
Functional 5-HT4 receptors have been reported to be present in numerous isolated tissue preparations including the rat oesophagus, guineapig ileum, and human colon. The pharmacological properties of the novel, potent and selective 5-HT4 receptor antagonists SB203186 (1-piperidinyl)ethyl 1H-indole 3-carboxylate, SB205008 (1-butyl-1-methyl4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate iodide, and SB207710 (1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4 benzodioxan-5… 
Comparison of 5-HT4 receptors in guinea-pig colon and rat oesophagus: effects of novel agonists and antagonists
Abstract5-HT4 receptors in isolated distal colon myenteric plexus of guinea-pig, mediating contraction of longitudinal smooth muscle, have been further characterized by selective agonists and
Changes in sensitivity of 5-HT receptor mediated functional responses in the rat oesophagus, fundus and jejunum following chronic infusion with 5-hydroxytryptamine
It is shown in a preliminary characterisation that in rat jejunum, 5-HT produces a biphasic concentration-effect curve which is mediated by a putative 5-ht7/5-HT3 receptor-mediated responses in rat oesophagus, fundus andJejunum respectively when measured in vitro.
Post-synaptic 5-HT4 receptor modulation of tachykinergic excitation of rat oesophageal tunica muscularis mucosae.
This study shows for the first time that although 5-HT4 receptors are involved in the modulation of cholinergic neurotransmission they can also act independently of this system modulating tachykinergic responsiveness.
5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-α]pyridine-8-carboxamide (CJ-033,466), a Novel and Selective 5-Hydroxytryptamine4 Receptor Partial Agonist: Pharmacological Profile in Vitro and Gastroprokinetic Effect in Conscious Dogs
CJ-033,466 is a potent and highly selective 5-HT4 agonist that stimulates physiologically coordinated gastric motility, and it has no activity on other 5- HT receptor subtypes and D2 receptors.
5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist.
It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal motility disorders in horses.
Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT4 receptors with SPET
Findings show that [123I]SB 207710 is an effective radioligand for imaging brain 5-HT4 receptors in vivo, compared with previous measures of 5- HT4 receptor density distribution in vitro.
Synthesis, structure-affinity relationships, and radiolabeling of selective high-affinity 5-HT4 receptor ligands as prospective imaging probes for positron emission tomography.
High-affinity ligands were discovered for recombinant human 5-HT(4) receptors with amenability to labeling with a positron emitter and potential for development as imaging probes.
5‐Hydroxytryptamine Receptor Assays
Tissue bath assays using vascular and smooth muscle tissues isolated from guinea‐pig, rat, and rabbit make possible the analyses of compounds at nine serotonin receptor subtypes and characterize serotonergic agonists and antagonists in physiologically relevant organ systems.
Effect of two artichoke extracts (36_U and 36_EB) on rat ileum (with respect to bowel syndrome) and the peristaltic threshold.
From the data it can be derived that the extract 36_U may be useful in IBS combined with obstipation when gastrointestinal contraction is necessary, whereas 36_EB may be helpful in Ibs combined with diarrhea when gastrointestinal relaxation is desired.
Pharmacological Basis for the Medicinal Use of Psyllium Husk (Ispaghula) in Constipation and Diarrhea
This study demonstrates that Ispaghula has a Gut-stimulatory effect, mediated partially by muscarinic and 5-HT4 receptor activation, which may complement the laxative effect of its fiber content, and a gut-inhibitory activity possibly mediated by blockade of Ca2+ channels and activation of NO-cyclic guanosine monophosphate pathways.


SDZ 205-557, a selective, surmountable antagonist for 5-HT4 receptors in the isolated guinea pig ileum
It is concluded that SDZ 205-557 is a potent, selective and surmountable antagonist at 5- HT4 receptors in the isolated guinea pig ileum, and is a more practical tool for the characterization of 5-HT4 receptors than ICS 205-930.
Pharmacological characterization of a neuronal receptor for 5-hydroxytryptamine in guinea pig ileum with properties similar to the 5-hydroxytryptamine receptor.
  • D. Craig, D. Clarke
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1990
Unlike Gaddum's M receptor, the putative 5-HT4 [corrected] receptor site exhibits a higher sensitivity to agonism by 5- HT and is resistant to antagonism by cocaine.
Identification of putative 5-HT4 receptors in guinea-pig ascending colon.
The pharmacological characteristics of the receptor, which mediates contraction of guinea-pig ascending colon by activation of cholinergic nerves, are consistent with it being of the putative 5-HT4 receptor type.
DAU 6285: a novel antagonist at the putative 5-HT4 receptor.
In the guinea-pig ileum, DAU 6285 (10 microM) did not exert antimuscarinic, antihistaminic, antinicotinic or myolytic activity, and may represent a suitable tool for studies in the field of 5-HT4 receptors.
A comparative study of functional 5‐HT4 receptors in human colon, rat oesophagus and rat ileum
The studies have shown that the human colon, rat oesophagus and rat ileum contain functional 5‐HT4 receptors and the 5‐ HT4 receptor agonists displayed differences in these tissues making it to be cautious when extrapolating from animal to human tissue.
Benzimidazolone derivatives: a new class of 5-hydroxytryptamine4 receptor agonists with prokinetic and acetylcholine releasing properties in the guinea pig ileum.
It is indicated that benzimidazolone derivatives act as agonists in the guinea pig ileum causing enhancement of acetylcholine release and peristaltic activity.
The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons
It is reported that this non-classical 5-HT receptor can be stimulated by 4-amino-5-chloro-2-methoxy substituted benzamide derivatives and is similar to the pharmacology of the high affinity 5- HT receptors involved in the indirect stimulation of smooth muscle in the guinea pig ileum.
5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae
Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, sugesting that 5- HT-induced relaxation of the tunica muscularis mucosae was mediated via a postjunctional receptor, independent of endogenous prostanoids.
A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system.
The relatively low affinity of this hippocampal receptor for 5-CT, its stimulation by RU 28253 but not by RU 24969, and its previously reported pharmacological characteristics support the contention that this 5- HT receptor and the 5-HT receptor of mouse embryo colliculi neurons in primary culture present great homologies.
Effect of the novel 5‐HT4 receptor agonist DAU 6236 in human colon
Clinical evaluation of 5-HT, agonists would be worthwhile in helping to determine whether they have specific therapeutic value in treating conditions of the colon, such as irritable bowel disease, in addition to their beneficial effects elsewhere in the alimentary tract.