Role of antispasmodics in the treatment of irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT_1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.

Keywords: Irritable bowel syndrome, Motility, Treatment, Calcium channel blockers, Spasmolytics

Core tip: Treatment of irritable bowel syndrome (IBS) must target intestinal motility alterations and visceral hypersensitivity. Antispasmodics have been used in the treatment of IBS for decades, and large placebo-controlled trials have recently been conducted on their efficacy. Alverine citrate, in combination with simethicone, effectively reduced abdominal pain and discomfort; while otilonium bromide also improved defecation problems. Pinaverium bromide regulated impaired motility and reduced stool complaints. Phloroglucinol and trimethylphloroglucinol reduced pain in IBS patients. Mebeverine was recently found to be effective only in non-placebo-controlled trials. Antispasmodics are considered safe. T-type calcium channel blockers could represent a future therapeutic option in IBS treatment.