Distribution of acotiamide, an orally active acetylcholinesterase inhibitor, into the myenteric plexus of rat and dog stomachs

• DOI: 10.1016/j.lfs.2015.12.020
• Publication Date: 2015-12-15T15:12:27Z
• Authors: Kazuyoshi Yoshii; Takashi Yamaguchi; Masamichi Hirayama; Ryoko Toda; Toshiko Kinomoto; Yoshihiro Kawabata; Kan Chiba
• Keywords: Male; 0301 basic medicine; Acotiamide; Functional dyspepsia; Biochemistry, Genetics and Molecular Biology(all); Stomach; Myenteric Plexus; Rats; 3. Good health; Rats, Sprague-Dawley; Pharmacology, Toxicology and Pharmaceutics(all); Thiazoles; 03 medical and health sciences; Dogs; Gastric Mucosa; Benzamides; Acetylcholinesterase; Animals; Stomach distribution; Cholinesterase Inhibitors; Dyspepsia

Acotiamide is the first-in-class drug for treatment of functional dyspepsia. Although pharmacological and therapeutic actions acotiamide are thought to be derived from its inhibitory effects on acetylcholinesterase (AChE), whether concentration at site action sufficient inhibit AChE remains unclear. Since major cholinergic nerve terminals in gastric myenteric plexus, we studied distribution [(14)C]acotiamide into plexus.Distribution was evaluated using macro- micro-autoradiography rats dogs.The results macro-autoradiography showed radioactivity 27.9μM rat stomach, which 12 times higher than IC50 AChE. Being different rats, muscular layer distinguishable that mucosal dog stomach. The stomach (1.41μM) approximately two-times lower those layer, however, it 1.2 also distributed homogenously suggesting around ganglion plexus similar stomach.These findings suggest distributes a putative action, with adequate concentrations AChE, both stomachs.