Law · American journal of physiology. Gastrointestinal and liver physiology 2001 · randomized controlled trial · n=30

Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans.

Cited 147 times in the scientific literature.

Level 2 - randomized trial

Randomized controlled physiological trial in human subjects.

PubMed 11668032 · doi:10.1152/ajpgi.2001.281.5.G1228 · record verified 2026-08-26

What was done

A barostat-manometric assembly evaluated descending colon and rectal phasic pressures, tone, compliance, and sensory perception to distension in 30 healthy volunteers randomized to receive intravenous neostigmine (0.25, 0.75, or 1.5 mg; n = 15) or subcutaneous bethanechol (2.5, 5, or 10 mg; n = 15). Scintigraphic assessment of colonic transit (geometric center) following neostigmine, bethanechol, or saline was subsequently conducted in 21 subjects.

What was found

Both neostigmine and bethanechol increased colonic phasic pressure activity, reduced rectal compliance, and heightened rectal urgency during distension. Neostigmine reduced balloon volumes, increasing colonic tone by an average of 12% and rectal tone by 25% at the 1.5 mg dose. Only neostigmine reduced colonic compliance, accelerated colonic transit (mean geometric center at 90 min: 2.5 vs. 1.0 with placebo), and increased colonic pain perception during distension.

Why it matters

These results provide a physiological rationale for neostigmine's efficacy in acute colonic pseudo-obstruction, demonstrating that broad cholinergic stimulation stimulates coordinated colonic propulsion and tone far more effectively than direct M2/M3 agonism.

Limits

The sample size was small and limited to healthy volunteers without gastrointestinal motility disorders. The two drugs were administered via different routes (intravenous vs. subcutaneous), introducing pharmacokinetic differences, and long-term efficacy or safety profiles were not assessed.

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