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

Journal of Pharmacology and Experimental Therapeutics

Volumn 325, Issue 1, 2008, Pages 190-199

  Mikami, Tadayoshi ^a   Ochi, Yasuo ^a   Suzuki, Keiko ^a   Saito, Toshiyuki ^a   Sugie, Yutaka ^a   Sakakibara, Minoru ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AMINO 6 CHLORO N [(1 ISOBUTYLPIPERIDIN 4 YL)METHYL] 2 METHYLIMIDAZO[1,2 ALPHA]PYRIDINE 8 CARBOXAMIDE; CISAPRIDE; CJ 033466; MOSAPRIDE CITRATE; PARTIAL AGONIST; SEROTONIN 4 AGONIST; TEGASEROD; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; DIET RESTRICTION; DOG; DOSE RESPONSE; DRUG ACTIVITY; DRUG EFFECT; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; EMBRYO; GASTROINTESTINAL MOTILITY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MALE; NONHUMAN; PHARMACODYNAMICS; PHARMACOLOGICAL PARAMETERS; POSTPRANDIAL STATE; PRIORITY JOURNAL; RAT; STOMACH EMPTYING; STOMACH PARESIS;

AMINOPYRIDINES; ANIMALS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; GASTRIC EMPTYING; GASTROINTESTINAL MOTILITY; GASTROPARESIS; HUMANS; IMIDAZOLES; RADIOLIGAND ASSAY; RATS; RECEPTORS, DOPAMINE D2; RECEPTORS, SEROTONIN, 5-HT4; SEROTONIN AGONISTS;

EID: 41149180692     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.107.133850     Document Type: Article

References (41)

1. Albibi R and McCallum RW (1983) Metoclopramide: pharmacology and clinical application. Ann Intern Med 98:86-95.
2. Bach T, Syversveen T, Kvingedal AM, Krobert KA, Brattelid T, Kaumann AJ, and Levy FO (2001) 5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle. Naunyn Schmiedebergs Arch Pharmacol 363:146-160.
3. Banères JL, Mesnier D, Martin A, Joubert L, Dumuis A, and Bockaert J (2005) Molecular characterization of a purified 5-HT4 receptor: a structural basis for drug efficacy. J Biol Chem 280:20253-20260.
4. Baxter GS, Craig DA, and Clarke DE (1991) 5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae. Naunyn Schmiedebergs Arch Pharmacol 343:439-446.
5. Beattie DT, Smith JA, Marquess D, Vickery RG, Armstrong SR, Pulido-Rios T, McCullough JL, Sandlund C, Richardson C, Mai N, et al. (2004) The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol 143:549-560.
6. Bockaert J, Claeysen S, Compan V, and Dumuis A (2004) 5-HT4 receptors. Curr Drug Targets CNS Neurol Disord 3:39-51.
7. Borman RA, Tilford NS, Harmer DW, Day N, Ellis ES, Sheldrick RL, Carey J, Coleman RA, and Baxter GS (2002) 5-HT(2B) receptors play a key role in mediating the excitatory effects of 5-HT in human colon in vitro. Br J Pharmacol 135:1144-1151.
8. Camilleri M (2001) Review article: tegaserod. Aliment Pharmacol Ther 15:277-289.
9. Chapple CR, Radley SC, Martin SW, Sellers DJ, and Chess-Williams R (2004) Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle. BJU Int 93:599-604.
10. Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108.
11. Costall B, Naylor RJ, and Tan CC (1984) Neuronally mediated contraction responses of guinea-pig stomach smooth muscle preparations: modification by benzamide derivatives does not reflect a dopamine antagonist action. Eur J Pharmacol 102:79-89.
12. Costedio MM, Hyman N, and Mawe GM (2007) Serotonin and its role in colonic function and in gastrointestinal disorders. Dis Colon Rectum 50:376-388.
13. Endo J, Nomura M, Morishita S, Uemura N, Inoue S, Kishi S, Kawaguchi R, Iga A, Ito S, and Nakaya Y (2002) Influence of mosapride citrate on gastric motility and autonomic nervous function: evaluation by spectral analyses of heart rate and blood pressure variabilities, and by electrogastrography. J Gastroenterol 37:888-895.
14. 4 receptor modulators. World patent WO03035649, 2003 May 1.
15. Gershon MD (2004) Review article: serotonin receptors and transporters - roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther 20 (Suppl 7):3-14.
16. Gershon MD and Tack J (2007) The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132:397-414.
17. Heading RC, Nimmo J, Prescott LF, and Tothill P (1973) The dependence of paracetamol absorption on the rate of gastric emptying. Br J Pharmacol 47:415-421.
18. Hiyama T, Yoshihara M, Matsuo K, Kusunoki H, Kamada T, Ito M, Tanaka S, Nishi N, Chayama K, and Haruma K (2007) Meta-analysis of the effects of prokinetic agents in patients with functional dyspepsia. J Gastroenterol Hepatol 22:304-310.
19. Hoyer D and Martin G (1997) 5-HT receptor classification and nomenclature: towards a harmonization with the human genome. Neuropharmacology 36:419-428.
20. 4 receptor agonists. World patent WO04026869. 2004 Apr 1.
21. Itoh Z, Honda R, Takeuchi S, Aizawa I, and Takayanagi R (1977) An extraluminal force transducer for recording contractile activity of the gastrointestinal smooth muscle in the conscious dogs: its construction and implantation. Gastroenterol Jpn 12:275-283.
22. Kahrilas PJ, Quigley EM, Castell DO, and Spechler SJ (2000) The effects of tegaserod (HTF 919) on oesophageal acid exposure in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 14:1503-1509.
23. Komada T and Yano S (2007) Pharmacological characterization of 5-hydroxytryptamine-receptor subtypes in circular muscle from the rat stomach. Biol Pharm Bull 30:508-513.
24. McCullough JL, Armstrong SR, Hegde SS, and Beattie DT (2006) The 5-HT2B antagonist and 5-HT4 agonist activities of tegaserod in the anaesthetized rat. Pharmacol Res 53:353-358.
25. McLean PG and Coupar IM (1995) 5-HT4 receptor antagonist affinities of SB207710, SB205008, and SB203186 in the human colon, rat oesophagus, and guinea-pig ileum peristaltic reflex. Naunyn Schmiedebergs Arch Pharmacol 352:132-140.
26. 4d receptor desensitization in CHO cells. Br J Pharmacol 138:445-452.
27. Mine Y, Yoshikawa T, Oku S, Nagai R, Yoshida N, and Hosoki K (1997) Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther 283:1000-1008.
28. Neal KB and Bornstein JC (2006) Serotonergic receptors in therapeutic approaches to gastrointestinal disorders. Curr Opin Pharmacol 6:547-552.
29. Prins NH, Akkermans LM, Lefebvre RA, and Schuurkes JA (2001) Characterization of the receptors involved in the 5-HT-induced excitation of canine antral longitudinal muscle. Br J Pharmacol 134:1351-1359.
30. Sakurai-Yamashita Y, Yamashita K, Kanematsu T, and Taniyama K (1999) Localization of the 5-HT(4) receptor in the human and the guinea pig colon. Eur J Pharmacol 383:281-285.
31. Sato F, Marui S, Inatomi N, Itoh Z, and Omura S (2000) EM574, an erythromycin derivative, improves delayed gastric emptying of semi-solid meals in conscious dogs. Eur J Pharmacol 395:165-172.
32. Schuurkes JA and Van Nueten JM (1984) Domperidone improves myogenically transmitted antroduodenal coordination by blocking dopaminergic receptor sites. Scand J Gastroenterol Suppl 96:101-110.
33. Schuurkes JA, Van Nueten JM, Van Daele PG, Reyntjens AJ, and Janssen PA (1985) Motor-stimulating properties of cisapride on isolated gastrointestinal preparations of the guinea pig. J Pharmacol Exp Ther 234:775-783.
34. Taniyama K, Makimoto N, Furuichi A, Sakurai-Yamashita Y, Nagase Y, Kaibara M, and Kanematsu T (2000) Functions of peripheral 5-hydroxytryptamine receptors, especially 5-hydroxytryptamine4 receptor, in gastrointestinal motility. J Gastroenterol 35:575-582.
35. Toga T, Kohmura Y, and Kawatsu R (2007) The 5-HT(4) agonists cisapride, mosapride, and CJ-033466, a Novel potent compound, exhibit different human ether-a-go-go-related gene (hERG)-blocking activities. J Pharmacol Sci 105:207-210.
36. Yamano M, Kamato T, and Miyata K (1997) Participation of a cholinergic mechanism in 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptor-mediated stimulation of gastric emptying in rats. Arzneimittelforschung 47:1242-1246.
37. Yoshida N (1999) [Pharmacological effects of the gastroprokinetic agent mosapride citrate]. Nippon Yakurigaku Zasshi 113:299-307.
38. Yoshida N, Ito T, Karasawa T, and Itoh Z (1991) AS-4370, a new gastrokinetic agent, enhances upper gastrointestinal motor activity in conscious dogs. J Pharmacol Exp Ther 257:781-787.
39. Yoshida N, Omoya H, Oka M, Furukawa K, Ito T, and Karasawa T (1989) AS-4370, a novel gastrokinetic agent free of dopamine D2 receptor antagonist properties. Arch Int Pharmacodyn Ther 300:51-67.
40. Yoshikawa T, Yoshida N, Mine Y, and Hosoki K (1998) Affinity of mosapride citrate, a new gastroprokinetic agent, for 5-HT4 receptors in guinea pig ileum. Jpn J Pharmacol 77:53-59.
41. Zar MA, Ebong O, and Bateman DN (1982) Effect of metoclopramide in guinea-pig ileum longitudinal muscle: evidence against dopamine-mediation. Gut 23:66-70.