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New insights into the characterization of the mechanism of action of hyoscine butylbromide in the human colon ex vivo.
Traserra, Sara; Alcalá-González, Luis Gerardo; Barber, Claudia; Landolfi, Stefania; Malagelada, Carolina; Lange, Robert; Forestier, Sylvie; Corsetti, Maura; Jimenez, Marcel.
Afiliación
  • Traserra S; Universitat Autònoma de Barcelona, Department of Cell Biology, Physiology and Immunology, Barcelona, Spain.
  • Alcalá-González LG; Vall D'Hebron University Hospital, Digestive System Research Unit, Barcelona, Spain.
  • Barber C; Vall D'Hebron University Hospital, Digestive System Research Unit, Barcelona, Spain.
  • Landolfi S; Valld'Hebron University Hospital, Department of Pathology, Barcelona, Spain.
  • Malagelada C; Vall D'Hebron University Hospital, Digestive System Research Unit, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
  • Lange R; Sanofi Frankfurt, Germany.
  • Forestier S; Formerly with Sanofi Gentilly, France.
  • Corsetti M; Nottingham University Hospitals NHS Trust and the University of Nottingham, NIHR Nottingham Biomedical Research Centre (BRC), Nottingham, United Kingdom; University of Nottingham, Nottingham Digestive Diseases Centre, Nottingham, United Kingdom.
  • Jimenez M; Universitat Autònoma de Barcelona, Department of Cell Biology, Physiology and Immunology, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain. Electronic address: marcel.jimenez@uab.es.
Eur J Pharmacol ; 972: 176550, 2024 Jun 05.
Article en En | MEDLINE | ID: mdl-38570081
ABSTRACT

INTRODUCTION:

Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways.

METHODS:

309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators.

RESULTS:

In the presence of tetrodotoxin (TTX), HBB and atropine 1 µM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses.

CONCLUSIONS:

This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bromuro de Butilescopolamonio / Colon / Contracción Muscular Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bromuro de Butilescopolamonio / Colon / Contracción Muscular Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Países Bajos