# A new drug their studing for IBS



## eric (Jul 8, 1999)

FYI J Pharmacol Exp Ther 2001 Aug 1;298(2):559-564 Books, LinkOut Effects of TAK-637, a Novel Neurokinin-1 Receptor Antagonist, on Colonic Function in Vivo. Okano S, Nagaya H, Ikeura Y, Natsugari H, Inatomi N. Pharmaceutical Discovery Research Division and Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan. Substance P (SP) is an important neurotransmitter that mediates various gut functions; however, its precise pathophysiological role remains unclear. In this study, we investigated the effect of SP on colonic function and the effect of TAK-637 {(aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g][1,7]naphthyridine-6,13-dione}, a new neurokinin-1 (NK(1)) receptor antagonist, on colonic responses to SP or stress in Mongolian gerbils. SP and the selective NK(1) agonist [pGlu(6)]SP(6-11) significantly increased fecal pellet output. TAK-637 reduced [pGlu(6)]SP(6-11)-induced defecation, but did not significantly affect neurokinin A-, 5-hydroxytryptamine- or carbachol-stimulated defecation. Oral TAK-637 decreased restraint stress-stimulated fecal pellet output with an ID(50) value of 0.33 mg/kg. Ondansetron and atropine, but not the peripheral kappa-receptor agonist trimebutine, also reduced restraint stress-stimulated defecation. TAK-637 inhibited the increase in fecal pellet output stimulated by intracerebroventricular injection of corticotropin-releasing factor, but did not affect the stress-induced increase in plasma adrenocorticotropic hormone levels. Denervation of the sensory neurons with capsaicin did not affect stress-stimulated defecation. These results suggest that NK(1) receptors in the enteric plexus play an important role in stress-induced changes in colonic function, and that TAK-637 may be useful in the treatment of functional bowel diseases such as irritable bowel syndrome. PMID: 11454917 [PubMed - as supplied by publisher] ------------------Moderator of the Cognitive Behavioral Therapy, Anxiety and Hypnotherapy forumI work with Mike and the IBS Audio Program. www.ibshealth.com www.ibsaudioprogram.com


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## atrain (Jun 22, 2001)

Is this drug going to be studied in the US for its possible use??


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## Kerri (Oct 1, 1999)

This drug has been under study in the US. Right now the studies have been halted pending further research. There were some animals that developed eye problems while on the drug. I spoke with a researcher from the company a couple of months ago and he told me that these eye problems did not occur in any of the humans in the trials. However, they were told by the FDA to stop the trials pending more studies into the eye problem. The researcher told me he'd call me if and when the trials were resumed. He was optimistic, but didn't know how long it would take.Kerri


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## eric (Jul 8, 1999)

A lot of research on drugs for IBS is under scrutiny right now and they are having problems and it has slowed down research.------------------Moderator of the Cognitive Behavioral Therapy, Anxiety and Hypnotherapy forumI work with Mike and the IBS Audio Program. www.ibshealth.com www.ibsaudioprogram.com


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