The effects of a novel metabotropic glutamate receptor 5 antagonist (AZD2066) on transient lower oesophageal sphincter relaxations and reflux episodes in healthy volunteers.
Aliment Pharmacol Ther
; 35(10): 1231-42, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22469098
ABSTRACT
BACKGROUND:
Selective metabotropic glutamate receptor 5 (mGluR5) antagonists inhibit transient lower oesophageal sphincter relaxations (TLESRs) in animals and acid reflux in humans.AIM:
To assess the effect of single doses of the mGluR5 antagonist AZD2066 on TLESRs and reflux in humans.METHODS:
Healthy male volunteers received AZD2066 13 mg and placebo (part A), or AZD2066 2 mg and AZD2066 6 mg and placebo (part B), in a randomised crossover study. Postprandial manometry/pH-impedance measurements were taken after each dose.RESULTS:
A total of 13 individuals completed part A of the study and 19 individuals completed part B. There was a significant reduction in the geometric mean number of TLESRs (27%; P = 0.02) and the geometric mean number of reflux episodes (51%; P = 0.01) in subjects receiving AZD2066 13 mg compared with placebo. Adverse events in participants receiving AZD2066 13 mg were mostly related to the nervous system [dizziness (3/13); disturbance in attention (3/13)]. Adverse events were reversible and of mild intensity. There were no serious adverse events. The effects of AZD2066 appeared dose-dependent, with smaller reductions in TLESRs and reflux episodes (relative to placebo) and fewer adverse events observed for AZD2066 2 mg and AZD2066 6 mg compared with AZD2066 13 mg.CONCLUSION:
The mGluR5-mediated inhibition of TLESRs may be a useful approach for inhibiting gastro-oesophageal reflux.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triazóis
/
Fármacos Gastrointestinais
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Refluxo Gastroesofágico
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Receptores de Glutamato Metabotrópico
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Esfíncter Esofágico Inferior
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Isoxazóis
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Humans
/
Male
Idioma:
En
Revista:
Aliment Pharmacol Ther
Ano de publicação:
2012
Tipo de documento:
Article