Document Detail


Effects of the peripherally acting NK receptor antagonist, SB-235375, on intestinal and somatic nociceptive responses and on intestinal motility in anaesthetized rats.
MedLine Citation:
PMID:  15086876     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated the effects of the selective NK(3) tachykinin receptor antagonist, SB-235375, on noxious signalling from gut and skin and on intestinal motility in anaesthetized rats. We also measured penetrance into brain and spinal cord. Nociceptive responses in reaction to colorectal distension and skin pinch were assessed by recording the electromyogram (EMG) from the external oblique muscle (a visceromotor response). Motility was measured by recording intraluminal pressure waves during changes in baseline pressure in the jejunum. Colorectal compliance was assessed by measuring luminal pressure change during isovolumic distension. SB-235375 (20 mg kg(-1), by i.v. bolus) reduced the EMG response to colorectal distension by over 90%. The reduction was slow at onset, peaked at about 60 min, and lasted for over 2 h. Responses to noxious skin pinch were unchanged. Amplitudes of propulsive waves in the jejunum were slightly reduced, but their frequency of occurrence was unchanged. SB-235375 decreased colorectal compliance by 5-10%. There was undetectable penetration of i.v. SB-235375 into brain or spinal cord. We conclude that SB-235375 acts peripherally to substantially reduce nociceptive signalling from colorectum without affecting noxious signalling from skin and with little effect on intestinal motility.
Authors:
A D Shafton; G Bogeski; P D Kitchener; V A Lewis; G J Sanger; J B Furness
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society     Volume:  16     ISSN:  1350-1925     ISO Abbreviation:  Neurogastroenterol. Motil.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-16     Completed Date:  2004-06-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9432572     Medline TA:  Neurogastroenterol Motil     Country:  England    
Other Details:
Languages:  eng     Pagination:  223-31     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
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MeSH Terms
Descriptor/Qualifier:
Acetic Acids / analysis,  pharmacokinetics,  pharmacology*
Anesthesia
Animals
Blood-Brain Barrier / physiology
Electromyography
Enteric Nervous System / physiology
Gastrointestinal Motility / drug effects*
Intestines / drug effects,  physiology*
Male
Nociceptors / drug effects,  physiology
Pain / physiopathology*
Quinolines / analysis,  pharmacokinetics,  pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Neurokinin-3 / antagonists & inhibitors*
Skin / innervation
Chemical
Reg. No./Substance:
0/Acetic Acids; 0/N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide; 0/Quinolines; 0/Receptors, Neurokinin-3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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