Effect of Selective and Non-Selective Antimuscarinics on Rectosigmoid Motility and Gastrointestinal Transit

Abstract

In 12 healthy volunteers, a rectosigmoid motility index (RSMI) was measured when either placebo, 0.5 mg atropine, or 5 mg pirenzepine was given intravenously as a single dose, double-blind, in random order after a control period of 30 min. Compared with the control period, atropine gave a significant decrease of the RSMI during the entire recorded period of 90 min, whereas pirenzepine inhibited RSMI only during the first two 15-min periods. In another series of experiments, gastrointestinal transit was assessed by means of a radiographic marker method. In healthy volunteers, gastrointestinal transit was estimated (n = 20) and gastric secretion was measured (basally and after modified sham feeding; n = 10) during oral medication with placebo, 50 mg pirenzepine twice daily, or 17.5 mg benzilonium bromide twice daily. In 10 of the volunteers gastrointestinal transit was also estimated with 35 mg benzilonium bromide twice daily, and in the other 10 volunteers with 0.6 mg L-hyoscyamine twice daily. The number of retained markers was significantly lower during pirenzepine than during L-hyoscyamine treatment. Neither dose of benzilonium bromide changed the transit of markers. Compared with non-selective antimuscarinics, the effect of pirenzepine was differential: with equipotently acid-reducing doses the decrease of the RSMI after pirenzepine lasted shorter and gastrointestinal transit was accelerated.

Model of rapid gastrointestinal transit in dogs: effects of muscarinic antagonists and a nitric oxide synthase inhibitor

“…Intravenous administration of pirenzepine (300 µg kg −1 ) delayed the MMC cycle in dogs 20 . On the other hand, low doses of pirenzepine (50 mg day −1 by mouth) stimulated gastrointestinal motility, while 50 mg twice daily accelerated gastrointestinal transit 21,22 in humans. The M 2 blocker, AF‐DX116 (300 µg kg −1 intravenously) decreased colonic tone in dogs 23 but 400 µg kg −1 intravenously did not slow gastric emptying or small bowel transit in rats 24 .…”

Enhancement of guinea‐pig intestinal peristalsis by blockade of muscarinic M1‐receptors

“…They suggested that the stimulation was probably central. However, the antagonist pirenzepine which does not cross the blood-brain barrier, may also accelerate gastro-intestinal transit time (Jaup et al, 1985) or increase the frequency of antral contractions (Stacher et al, 1982) in man. Pirenzepine has a higher affinity for Ml-muscarinic receptors than for M2-receptors, whereas atropine or hyoscine do not discriminate between both subtypes (for review see Birdsall & Hulme, 1985).…”

Accuracy in assessment of colonic transit time with particles: how many markers should be used?

“…a relatively high radiation dose 1–3 . In an attempt to reduce the radiation load, a modification has been tried with ingestion of a daily dose of particles for 3 days and a single abdominal X‐ray on day 4 4–6 . However, this principle cannot accurately differ between normal and delayed transit in women since healthy women may have CTT exceeding 4 days so that all particles are retained on day 4.…”