An orally active motilin receptor antagonist, MA-2029, inhibits motilin-induced gastrointestinal motility, increase in fundic tone, and diarrhea in conscious dogs without affecting gastric emptying

European Journal of Pharmacology

Volumn 615, Issue 1-3, 2009, Pages 185-192

  Ozaki, Ken ichi ^a   Onoma, Mitsu ^a   Muramatsu, Hiroyasu ^a   Sudo, Hirokazu ^a   Yoshida, Shoshin ^a   Shiokawa, Rie ^a   Yogo, Kenji ^a   Kamei, Kenshi ^a   Cynshi, Osamu ^a   Kuromaru, Osamu ^a   Peeters, Theo L ^b   Takanashi, Hisanori ^a  

^a CHUGAI PHARMACEUTICAL CO LTD   (Japan)

^b UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Diarrhea; Fundic tone; Hypermotility; MA 2029; Motilin receptor antagonist

Indexed keywords

HORMONE RECEPTOR BLOCKING AGENT; MA 2029; MOTILIN; N [2 (3 TERT BUTYL 4 HYDROXYPHENYL) 1 ETHYLCARBAMOYLETHYL] 3 METHYL 2 [METHYL (2 METHYLAMINO 3 PHENYLPROPIONYL)AMINO]BUTYRAMIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIARRHEA; DOG; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG MECHANISM; FEMALE; GASTROINTESTINAL MOTILITY DISORDER; INTESTINE CONTRACTION; MALE; NONHUMAN; PRIORITY JOURNAL; SMOOTH MUSCLE TONE; STOMACH EMPTYING; STOMACH VOLUME;

ADMINISTRATION, ORAL; ANIMALS; DIARRHEA; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GASTRIC EMPTYING; GASTRIC FUNDUS; GASTROINTESTINAL AGENTS; GASTROINTESTINAL MOTILITY; MALE; MOTILIN; MUSCLE CONTRACTION; MUSCLE TONUS; MUSCLE, SMOOTH; OLIGOPEPTIDES; RECEPTORS, GASTROINTESTINAL HORMONE; RECEPTORS, NEUROPEPTIDE;

EID: 67449132097     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2009.04.059     Document Type: Article

References (27)

1. Bormans V., Peeters T.L., and Vantrappen G. Motilin receptors in rabbit stomach and small intestine. Regul. Pept. 15 (1986) 143-153
2. Brown J.C., Mutt V., and Dryburgh J.R. The further purification of motilin, a gastric motor activity stimulating polypeptide from the mucosa of the small intestine of hogs. Can. J. Physiol. Pharm. 49 (1971) 399-405
3. Cuomo R., Vandaele P., Coulie B., Peeters T., Depoortere I., Janssens J., and Tack J. Influence of motilin on gastric fundus tone and on meal-induced satiety in man: role of cholinergic pathways. Am. J. Gastroenterol. 101 (2006) 804-811
4. Fukudo S., and Suzuki J. Colonic motility, autonomic function, and gastrointestinal hormones under psychological stress on irritable bowel syndrome. Tohoku J. Exp. Med. 151 (1987) 373-385
5. Heading R.C., Nimmo J., Prescott L.F., and Tothill P. The dependence of paracetamol absorption on the rate of gastric emptying. Br. J. Pharmacol. 47 (1973) 415-421
6. Itoh Z. Motilin and clinical application. Peptides 18 (1997) 593-608
7. Itoh Z., and Sekiguchi T. Interdigestive motor activity in health and disease. Scand. J. Gastroenterol. 82 Suppl. 18 (1983) 121-134
8. Kamerling I.M., van Haarst A.D., Burggraaf J., de Kam M., Biemond I., Jones R., Cohen A.F., and Masclee A.A. Exogenous motilin affects postprandial proximal gastric motor function and visceral sensation. Dig. Dis. Sci. 47 (2002) 1732-1736
9. Kamerling I.M., Van Haarst A.D., Burggraaf J., Schoemaker R.C., Biemond I., Heinzerling H., Jones R., Cohen A.F., and Masclee A.A. Motilin effects on the proximal stomach in patients with functional dyspepsia and healthy volunteers. Am. J. Physiol.: Gasterointest. Liver Physiol. 284 (2003) G776-781
10. Longstreth G.F., Thompson W.G., Chey W.D., Houghton L.A., Mearin F., and Spiller R.C. Functional bowel disorders. Gastroenterology 130 (2006) 1480-1491
11. McCallum R.W., and Cynshi O. Clinical trial: effect of mitemcinal (a motilin agonist) on gastric emptying in patients with gastroparesis - a randomized, multicentre, placebo-controlled study. Aliment. Pharmacol. Ther. 26 (2007) 1121-1130
12. McCallum R.W., and Cynshi O. Efficacy of mitemcinal, a motilin agonist, on gastrointestinal symptoms in patients with symptoms suggesting diabetic gastropathy: a randomized, multi-center, placebo-controlled trial. Aliment. Pharmacol. Ther. 26 (2007) 107-116
13. Mertz H., Naliboff B., Munakata J., Niazi N., and Mayer E.A. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 109 (1995) 40-52
14. Meulemans A.L., Eelen J.G., and Schuurkes J.A. NO mediates gastric relaxation after brief vagal stimulation in anesthetized dogs. Am. J. Physiol. 269 (1995) G255-261
15. Miller P., Trudel L., St-Pierre S., Takanashi H., and Poitras P. Neural and muscular receptors for motilin in the rabbit colon. Peptides 21 (2000) 283-287
16. Naliboff B.D., Munakata J., Fullerton S., Gracely R.H., Kodner A., Harraf F., and Mayer E.A. Evidence for two distinct perceptual alterations in irritable bowel syndrome. Gut 41 (1997) 505-512
17. Ohshiro H., Nonaka M., and Ichikawa K. Molecular identification and characterization of the dog motilin receptor. Regul. Pept. 146 (2008) 80-87
18. Ozaki K., Yogo K., Sudo H., Onoma M., Kamei K., Akima M., Koga H., Itoh Z., Ōmura S., and Takanashi H. Effects of mitemcinal (GM-611), an acid-resistant nonpeptide motilin receptor agonist, on the gastrointestinal contractile activity in conscious dogs. Pharmacology 79 (2007) 223-235
19. Ozaki K., Sudo H., Muramatsu H., Yogo K., Kamei K., Koga H., Itoh Z., Ōmura S., and Takanashi H. Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs. Inflammopharmacology 15 (2007) 36-42
20. Penning C., Gielkens H.A.J., Hemelaar M., Delemarre J.B.V.M., Bemelman W.A., Lamers C.B.H.W., and Masclee A.A.M. Prolonged ambulatory recording of antroduodenal motility in slow-transit constipation. Br. J. Surg. 87 (2000) 211-217
21. Poitras P., Miller P., Dickner M., Mao Y.K., Daniel E.E., St-Pierre S., and Trudel L. Heterogeneity of motilin receptors in the gastrointestinal tract of the rabbit. Peptides 17 (1996) 701-707
22. Rasmussen L., Oster-Jørgensen E., Qvist N., Holst J.J., Rehfeld J.F., Hovendal C.P., and Pedersen S.A. The relationship between gut hormone secretion and gastric emptying in different phase of the migrating motor complex. Scand. J. Gastroenterol. 31 (1996) 458-462
23. Simrén M., Abrahamsson H., and Bjornsson E.S. An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome. Gut 48 (2001) 20-27
24. Simrén M., Bjornsson E.S., and Abrahamsson H. High interdigestive and postprandial motilin levels in patients with the irritable bowel syndrome. Neurogastroenterol. Motil. 17 (2005) 51-57
25. Sudo H., Yoshida S., Ozaki K., Muramatsu H., Onoma M., Yogo K., Kamei K., Cynshi O., Kuromaru O., Peeters T.L., and Takanashi H. Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits. Eur. J. Pharmacol. 581 (2008) 296-305
26. Tack J., Piessevaux H., Coulie B., Caenepeel P., and Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 115 (1998) 1346-1352
27. Vantrappen G., Janssens J., Peeters T.L., Bloom S.R., Christofides N.D., and Hellemans J. Motilin and the interdigestive migrating motor complex in man. Dig. Dis. Sci. 24 (1979) 497-500