Acotiamide: a novel drug for the treatment of patients with functional dyspepsia
Keywords:Acotiamide, Acetylcholine, Functional dyspepsia
Functional dyspepsia (FD) is a highly prevalent condition with major socioeconomic and healthcare impact. Previously, no pharmacotherapeutic agent had approved for the treatment of this condition. Acotiamide, a new first-in-class oral prokinetic drug, is an upper gastrointestinal motility modulator for the treatment of abdominal symptoms resulting from hypomotility and delayed gastric emptying in patients with functional dyspepsia. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Unlike other prokinetic drugs that are utilized in the management of functional dyspepsia, acotiamide shows little/no affinity for serotonin or dopamine D2 receptors. Acotiamide is the world’s first approved treatment for functional dyspepsia diagnosed by Rome III criteria, with its first approval occurring in Japan. A favourable clinical course with acotiamide 100mg t.i.d was demonstrated with high symptom elimination rate for patients of FD.
Kumar A, Pate J, Sawant P. Epidemiology of functional dyspepsia. J Assoc Physicians India. 2012 Mar;60:9-12.
Loyd RA, MCClellan DA. Update on the evaluation and management of functional dyspepsia. American family physician. 2011 Mar 1;83(5):547.
Kawachi M, Matsunaga Y, Tanaka T. Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats. Eur. J. Pharmacol. Mechanistic study providing evidence of cholinesterase inhibitory effects of acotiamide in an animal model. 2011;666(1-3):218-25.
Matsunaga Y, Tanaka T, Yoshinaga K. Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther. 2011;336(3):791-800.
Adam B, Liebregts T, Zschau NB. Z-338 improves meal-induced symptoms in functional dyspepsia: a double-blind, randomized, placebo controlled crossover study. Gastroenterology. 2009;136:A535.
Kawachi M, Hori N, Takei M, Kurimoto T, Akaike N, Ito Y. Gastric relaxation induced by electrical and chemical stimulation of the area postrema in the rat. Gen. Physiol. Biophys. 2008;27(4):243-52.
Kusunoki H, Haruma K, Manabe N. Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography. Neurogastroenterol. Motil. 2012;24(6):540-5,e250.
Tack J, Masclee A, Heading R. A dose-ranging, placebo-controlled, pilot trial of acotiamide in patients with functional dyspepsia. Neurogastroenterol. Motil. 2009;21(3):272-80.
Talley NJ, Colin-Jones D, Koch KL, Nyren O, Stanghellini V. Functional dyspepsia. A classification with guidelines for diagnosis and management. Gastroenterol. Int. 4; 1991:145-160.
Tack J, Talley NJ, Camilleri M. Functional gastroduodenal disorders. Gastroenterology. 2006;130(5):1466-79.
Matsueda K, Hongo M, Tack J, Saito Y, Kato H. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012;61(6):821-8.
Matsueda K, Hongo M, Ushijima S, Akiho H. A long-term study of acotiamide in patients with functional dyspepsia: results from an open-label Phase III trial in Japan on efficacy, safety and pattern of administration. Digestion. 2011;84(4):261-8.