5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]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

The Journal of Pharmacology and Experimental Therapeutics
Tadayoshi MikamiMinoru Sakakibara

Abstract

5-Hydroxytryptamine (5-HT) receptors and dopamine(2) (D(2)) receptor modulate gastrointestinal motility. Gastroprokinetic agents that act on several 5-HT receptor subtypes and/or D(2) receptors are used clinically. Although the 5-HT(4) receptor is known to mediate the gastroprokinetic effects of these agents, the absence of highly selective 5-HT(4) receptor agonists has made it difficult to confirm the physiological consequences of selective 5-HT(4) receptor stimulation. In this study, we report the in vitro pharmacological profiles and the in vivo gastroprokinetic effects of 5-amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel, potent, and selective 5-HT(4) partial agonist. Compared with preceding 5-HT(4) agonists such as cisapride, mosapride, and tegaserod, CJ-033,466 had a superior in vitro profile, with nanomolar agonistic activities for the 5-HT(4) receptor and 1000-fold greater selectivity for the 5-HT(4) receptor over other 5-HT and D(2) receptors. In vivo studies in conscious dogs showed that CJ-033,466 dose-dependently stimulated gastric antral motility in both the fasted and postprandial states at the same dose range and that it was 30 times more ...Continue Reading

References

Feb 1, 1973·British Journal of Pharmacology·R C HeadingP Tothill
Jan 1, 1983·Annals of Internal Medicine·R Albibi, R W McCallum
Jun 25, 1998·Japanese Journal of Pharmacology·T YoshikawaK Hosoki
Sep 10, 1999·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·N Yoshida
Dec 14, 1999·European Journal of Pharmacology·Y Sakurai-YamashitaK Taniyama
Nov 9, 2000·Alimentary Pharmacology & Therapeutics·P J KahrilasS J Spechler
Feb 24, 2001·Alimentary Pharmacology & Therapeutics·M Camilleri
Feb 6, 2003·British Journal of Pharmacology·Jeanne MialetFrank Lezoualc'h
Feb 18, 2004·Current Drug Targets. CNS and Neurological Disorders·J BockaertA Dumuis
Oct 7, 2004·British Journal of Pharmacology·D T BeattieP P A Humphrey
Mar 19, 2005·The Journal of Biological Chemistry·Jean-Louis BanèresJoel Bockaert
Feb 24, 2006·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·J L McCulloughD T Beattie
Sep 16, 2006·Current Opinion in Pharmacology·Kathleen Bronwyn Neal, Joel Charles Bornstein
Jan 2, 2007·Diseases of the Colon and Rectum·Meagan M CostedioGary M Mawe
Feb 14, 2007·Journal of Gastroenterology and Hepatology·Toru HiyamaKen Haruma
Mar 3, 2007·Biological & Pharmaceutical Bulletin·Tohru Komada, Shingo Yano

❮ Previous
Next ❯

Citations

May 25, 2011·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Yoshitaka ToyomasuHiroyuki Kuwano
Dec 17, 2009·Journal of Gastroenterology·Masahiko FujisawaHiroshi Ozaki
Sep 15, 2010·Expert Opinion on Investigational Drugs·Ola GhaithAla I Sharara
Aug 19, 2016·The Journal of Pharmacology and Experimental Therapeutics·Ikumi Ishibashi-ShiraishiTatsuro Tanaka
Nov 29, 2017·The Journal of Pharmacology and Experimental Therapeutics·Nobuyuki Takahashi, Yukinori Take
Nov 15, 2011·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·P A BoakyeO B Balemba
Dec 17, 2016·The Journal of Organic Chemistry·S M Abdul ShakoorRajeev Sakhuja

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.