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Ebastine reduces symptoms in patients with IBS
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Ebastine, a histamine receptor H1 antagonist, was found to reduce visceral hypersensitivity, symptoms and abdominal pain in patients with irritable bowel syndrome in a recent study.
Based on previous data, “we hypothesized that visceral hypersensitivity in IBS results from TRPV1 sensitization induced by mast cell mediators, in particular by histamine,” Guy E. Boeckxstaens, MD, PhD, from the department of clinical and experimental medicine, Translational Research Center for Gastrointestinal Disorders, University Hospital Leuven, Belgium, and colleagues wrote.
Guy E. Boeckxstaens
First, Boeckxstaens and colleagues used live calcium imaging to compare the response of submucosal neurons to capsaicin in rectal biopsies from nine patients with IBS and 15 healthy volunteers. They also compared sensitization of TRPV1 by histamine, its metabolite imidazole acetaldehyde, and supernatants from biopsies using calcium imaging of mouse dorsal root ganglion neurons.
The results indicated that “in IBS patients, histamine released in the gut makes TRPV1 hypersensitive,” according to a press release. “The researchers found that histamine interferes with the histamine 1 receptor, which is located on nerves that contain TRPV1. Importantly, they discovered that blocking the histamine 1 receptor prevents the sensitizing effect of histamine on TRPV1. Taken together, these findings identify the mechanism behind IBS patients’ increased pain perception.”
Based on those results, the researchers then performed a double blind, proof-of-concept trial of ebastine, a histamine receptor H1 (HRH1) antagonist indicated for allergic rhinitis and chronic idiopathic urticarial. After a 2-week run-in period, patients with IBS (mean age, 31 years; range, 18-65 years) were randomly assigned 20 mg ebastine per day (n = 28) or placebo (n = 27) for 12 weeks, and were then followed up for an additional 2 weeks.
They used the validated Gastrointestinal Symptom Rating Scale to evaluate patient symptoms before and after the study period, and they assessed abdominal pain, symptom relief and health-related quality of life weekly. They also collected rectal biopsies after an initial rectal barostat study, and before and after the treatment period. Ebastine’s effect on symptom score evoked by rectal distension served as the primary endpoint.
At week 12, patients showed higher reductions in visceral hypersensitivity and symptoms (46% vs. 13%; P = .024), as well as abdominal pain scores (mean change, –17 ± 25 vs. 3 ± 23; P = .0004), compared with placebo.
“This is the first evidence … showing that TRPV1 is sensitized in IBS patients,” the researchers concluded. “This effect is mediated via HRH1 activation by histamine and its metabolite imidazole acetaldehyde and may lead to increased visceral pain perception in at least a subgroup of patients. Moreover, it provides the first demonstration that peripheral HRH1 antagonism can serve as a new treatment for IBS, resulting in a reduction of symptoms and improved quality of life.” – by Adam Leitenberger
Disclosure: The researchers report no relevant financial disclosures.
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