Screening of Antidiarrhoeal Drugs

Introduction & two-limb framework

• Definition — Antidiarrhoeal screening = the battery of in vivo and in vitro preclinical assays that detect and quantify a compound's ability to normalise experimentally-induced diarrhoea, acting on one or both of the two limbs generating diarrhoea — intestinal hypersecretion (fluid/electrolyte) and hypermotility (accelerated propulsion).
• Two diarrhoeogen families — the model must match the mechanism probed — secretory inducers (prostaglandins/PGE₂ & 16,16-dimethyl-PGE₂, castor oil → ricinoleic acid, MgSO₄, bile salts, cholera toxin, carbachol) vs motility/propulsion accelerators (sennosides & stimulant laxatives that speed large-intestinal transit).
• Two-limb readout — a valid assay should discriminate the antisecretory component from the antipropulsive (antimotility) component — a drug can be antipropulsive without being antisecretory (some opioids); the castor-oil rat test was explicitly proposed as an in vivo method able to evaluate both (Niemegeers 1984).
• Three functional headings (Vogel Part XI) — assays cluster as Intestinal Secretion (laxative activity, enteropooling, Ussing-chamber Cl^- secretion), Composite antidiarrhoeal effect (castor-oil, cecectomised-rat, cold-restraint) and Gut motility (isolated ileum, charcoal-meal transit, colon motility).
• Scope — this is experimental evaluation & screening only — models, apparatus, inducers, endpoints, reference standards; the clinical pharmacotherapy of antidiarrhoeals (drug classes, doses, ADRs) is a separate clinical topic and is deliberately out of scope.