Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transient lower esophageal sphincter relaxation is the major cause of gastroesophageal reflux. Mechanisms underlying transient lower esophageal sphincter relaxation are poorly understood although gastric mechanosensitive vagal afferent pathways play a central role. Glutamate is a key transmitter of vagal afferents acting partly on NMDA receptors. The aim of this work was to study the effects on transient lower esophageal sphincter relaxation in awake dogs (n=5) of the competitive NMDA receptor antagonist cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755; 0.3 and 3 mg/kg i.v., the high dose was given at two separate occasions to each dog). Transient lower esophageal sphincter relaxations were evoked by intragastric infusion of a liquid meal followed by air insufflation and were scored during a 45-min period. Neither dose produced any significant effect on the group average number of transient lower esophageal sphincter relaxations. Synchronous contractions of the esophagus were commonly seen during transient lower esophageal sphincter relaxation and CGS 19755 at both doses greatly reduced their occurrence. The findings indicate that NMDA receptor antagonism selectively inhibits the esophageal component of transient lower esophageal sphincter relaxation although the rate of transient lower esophageal sphincter relaxations is not consistently affected.
 ...
PMID:Effects of antagonism of NMDA receptors on transient lower esophageal sphincter relaxations in the dog. 1172 33

Metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) have previously been implicated in a number of pathophysiological conditions, based on preclinical, and to some extent clinical, proof of concept for migraine, gastroesophageal reflux disease, Parkinson's disease and anxiety. In the past, the potential use of known mGlu5 antagonists for the treatment of lower urinary tract disorders was disclosed. In the patent evaluated herein, novel derivatives of 4-(prop-2-ynylidene)piperidine are described and claimed by Recordati Ireland Ltd, Ireland, as NAMs at mGlu5 for the treatment of lower urinary tract disorders. Selected compounds reported in this application were efficacious in the cystometry model of bladder dysfunction in conscious rats, and mGlu5 NAMs are, therefore, suggested to have potential for the treatment of lower urinary tract disorders.
 ...
PMID:Novel heterocyclic compounds as mGlu5 antagonists: WO2009015897. 2018 Jun 23