Document Detail


A novel tachykinin NK2 receptor antagonist prevents motility-stimulating effects of neurokinin A in small intestine.
MedLine Citation:
PMID:  11522614     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. MEN 11420 (nepadutant) is a potent, selective and competitive antagonist of tachykinin NK2 receptors. 2. The objective of the present study was to assess the capability of the drug to antagonize the stimulatory effects of neurokinin A (NKA) on gastrointestinal motility, as well as to change the fasting migrating motor complex (MMC). 3. Thirty-four male volunteers were randomized to treatment with either placebo or MEN 11420 in a double-blinded manner. Effects of MEN 11420 (8 mg intravenously) were evaluated as changes in phases I, II and III of MMC, as well as contraction frequency, amplitude and motility index during baseline conditions and during stimulation of motility using NKA (25 pmol kg(-1) min(-1) intravenously). 4. NKA preceded by placebo increased the fraction of time occupied by phase II, increased contraction frequency, amplitude and motility index. 5. MEN 11420 effectively antagonized the motility-stimulating effects of NKA. MEN 11420 reduced the phase II-stimulating effect of NKA. In addition, the stimulatory effect of NKA on contraction frequency and amplitude, as well as motility index were inhibited by MEN 11420. MEN 11420 did not affect the characteristics of MMC during saline infusion. 6. Plasma levels of MEN 11420 peaked during the first hour after infusion and decreased to less than half during the first 2 h. 7. In conclusion, intravenous MEN 11420 effectively inhibited NKA-stimulated, but not basal gastrointestinal motility, and was well tolerated by all subjects.
Authors:
M Lördal; G Navalesi; E Theodorsson; C A Maggi; P M Hellström
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  134     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-08-27     Completed Date:  2001-10-11     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  215-23     Citation Subset:  IM    
Affiliation:
Department of Medicine, Section of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Abdominal Pain / chemically induced
Adolescent
Adult
Double-Blind Method
Flushing / chemically induced
Gastrointestinal Motility / drug effects*
Headache / chemically induced
Humans
Infusions, Intravenous
Intestine, Small / drug effects*,  physiology
Male
Middle Aged
Muscle Contraction / drug effects
Myoelectric Complex, Migrating / drug effects
Nausea / chemically induced
Neurokinin A / adverse effects,  blood,  pharmacology*
Peptides, Cyclic / adverse effects,  blood,  pharmacology*
Receptors, Neurokinin-2 / antagonists & inhibitors*,  physiology
Sodium Chloride / pharmacology
Time Factors
Vomiting / chemically induced
Chemical
Reg. No./Substance:
0/MEN 11420; 0/Peptides, Cyclic; 0/Receptors, Neurokinin-2; 7647-14-5/Sodium Chloride; 86933-74-6/Neurokinin A
Comments/Corrections

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