Pharmacological profile of YM-31636, a novel 5-HT3 receptor agonist, in vitro.

Abstract

We investigated the in vitro pharmacological profile of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate). In cloned human 5-HT3A receptors, YM-31636 had a pKi value of 9.67 vs. ramosetron and pKi values for other 5-HT3 receptor agonists were less than 7. YM-31636 showed very low affinities for other receptors. YM-31636 induced contraction of isolated guinea pig distal colon. The intrinsic activity was approximately 0.90 compared with 5-hydroxytryptamine's (5-HT) 1.0, and the potency was 26 times greater than that of 5-HT. YM-31636 increased short-circuit current (Isc) in the isolated guinea pig distal colon. In this case, the relative intrinsic activity was approximately 0.19. In isolated guinea pig right atrium, YM-31636 induced tachycardia with the relative intrinsic activity of approximately 0.23. All these effects of YM-31636 were antagonized by ramosetron, a selective 5-HT3 receptor antagonist. These results suggest that YM-31636 is a potent and selective 5-HT3 receptor agonist, preferentially acting on the contraction of the colon.

• Authors: H Ito, T Kiso, K Miyata, T Kamato, H Yuki, S Akuzawa, Y Nagakura, M Yamano, M Suzuki, Y Naitoh, H Sakai, K Iwaoka, T Yamaguchi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 409 Issue 2 Pg. 195-201 (Dec 08 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11104834 (Publication Type: Journal Article)

Chemical References

• 2-(1H-imidazol-4-ylmethyl)-8H-indeno(1,2-d)thiazole
• Anthraquinones
• Biguanides
• Pyrroles
• Receptors, Serotonin
• Receptors, Serotonin, 5-HT3
• Serotonin Receptor Agonists
• Thiazoles
• Serotonin
• 2-methyl-5-HT
• 1-(3-chlorophenyl)biguanide
• Dinoprostone
• Acetylcholine
• rhein

Topics

• Acetylcholine (pharmacology)
• Action Potentials (drug effects)
• Animals
• Anthraquinones (pharmacology)
• Atrial Function
• Biguanides (metabolism, pharmacology)
• Binding, Competitive
• Colon (drug effects, physiology)
• Dinoprostone (pharmacology)
• Dose-Response Relationship, Drug
• Guinea Pigs
• Heart Atria (drug effects)
• Humans
• In Vitro Techniques
• Muscle Contraction (drug effects)
• Myocardial Contraction (drug effects)
• Pyrroles (pharmacology)
• Receptors, Serotonin (drug effects, metabolism)
• Receptors, Serotonin, 5-HT3
• Serotonin (analogs & derivatives, metabolism, pharmacology)
• Serotonin Receptor Agonists (metabolism, pharmacology)
• Thiazoles (pharmacology)