Theme

Preclinical motility pharmacology

Acotiamide: oral prokinetic signal for meal-related dyspeptic motility impairment

Source
Source: Uploaded DOCX contains a Russian translation/excerpt of a Neurogastroenterology & Motility article by Nagahama et al. on acotiamide (Z-338) and gastrointestinal motility in conscious dogs. No named clinical trial, DOI, or URL is provided in the extracted text.

Acotiamide is an orally active prokinetic that boosts post-meal gastrointestinal motility in conscious dogs, mainly by inhibiting gastric acetylcholinesterase and enhancing cholinergic signaling.

Clinical question
Can cholinergic amplification restore impaired postprandial motility?
  Population
Conscious dogs with implanted force transducers
  Design
Preclinical GI motility pharmacology models
  Intervention
Oral acotiamide; intraduodenal mechanistic testing
  Readout window
Postprandial motility assessed up to 4 hours
  Comparators / challenges
Reference prokinetics; clonidine hypokinesia; atropine blockade
Hero finding

Restored antral motility under hypokinesia challenge

23.8%
motility remaining with clonidine-induced gastric hypokinesia
≈ normal
antral motility after acotiamide 10 mg/kg
p < 0.001
versus control

Model: clonidine-induced gastric hypokinesia. Baseline-normalized motility fell sharply, then recovered to approximately baseline with acotiamide 10 mg/kg.

Baseline-normalized antral motility

Why it matters

Functional dyspepsia is linked to impaired gastric and duodenal motility. A prokinetic that is orally active and mechanistically grounded could be especially relevant for post-meal symptoms.

What acotiamide does

Oral acotiamide increased postprandial motility in the gastric antrum, duodenum, and colon, with the strongest sustained signal in the antrum.

Key findings

Three data points clinicians should notice

Broad post-meal prokinetic effect
30
mg/kg oral dose
4 h
antral motility increased
2 h
duodenal + colonic signal
Gastric antrum0–4 h
Duodenum0–2 h
Colon0–2 h

Duration bars show the stated post-feeding window with significant motility increase.

Mechanism confirmed: acetylcholinesterase inhibition
7.25 ± 0.63
control nmol/min/mg protein
4.34 ± 0.22
after intraduodenal acotiamide
−40%
approximate reduction; p < 0.01
Cholinergic dependence: atropine blocks response
209.7 ± 15.8%
antral motility with acotiamide
15.9 ± 2.7%
after atropine
How it compares / holds up

Efficacy signal is durable and benchmarked

≥ reference
Matched or exceeded reference prokinetics in key models
No tachyphylaxis
Effect maintained after repeated dosing
Atropine-sensitive
Response depends on intact muscarinic cholinergic signaling
Numbers to know

A compact evidence dashboard

23.8%
clonidine hypokinesia motility vs baseline
≈ normal
restored with acotiamide 10 mg/kg
−40%
gastric antral AChE activity after intraduodenal dosing
4 h
significant postprandial antral motility increase at 30 mg/kg
209.7%
acotiamide-induced antral motility vs baseline
15.9%
remaining after atropine blockade

Takeaway: Position acotiamide as a mechanistically supported, orally active gastric prokinetic candidate for functional dyspepsia, especially meal-related symptoms linked to impaired gastric/duodenal motility — with the caveat that these preclinical dog data support, not replace, clinical evidence.

AbbreviationsQuick
Abbreviations: АХ/ACh — acetylcholine; АХЭ/AChE — acetylcholinesterase; ФД — functional dyspepsia; 5-HT4 — serotonin 5-HT4 receptor; D2 — dopamine D2 receptor; p.o. — oral; i.d. — intraduodenal; i.v. — intravenous; s.c. — subcutaneous.
Bibliography2
  1. Nagahama K, Matsunaga Y, Kawachi M, Ito K, Tanaka T, Hori Y, Oka H, Takei M. Acotiamide, a new orally active acetylcholinesterase inhibitor, stimulates gastrointestinal motor activity in conscious dogs. Neurogastroenterology & Motility.
  2. Tack J, Masclee A, Heading R et al. A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia. Neurogastroenterol Motil 2009;21:272–80.
✔Числа сверены с источником · Numbers verified against source