The selectivity of the (−)‐and (+)‐forms of hyoscine methiodide and of hyoscyamine camphorsulphonate for muscarinic (M₂) receptors

Abstract

1 The affinities of(-)-S-hyoscyamine (+ )-camphorsulphonate, (+ )-R-hyoscyamine (-)-camphorsulphonate, (-)-S-hyoscine methiodide and (+ )-R-hyoscine methiodide for muscarinic acetylcholine receptors in guinea-pig atria and ileum at 30°C and in ileum at 37°C have been measured in dose-ratio experiments. The agonists were carbachol, arecaidine propargyl ester (APE) and ethoxyethyl trimethylammonium iodide (EOE). 2 The effects produced by the agonists confirmed that, relative to carbachol, arecaidine propargyl ester is more active on atria than on ileum whereas ethoxyethyl trimethylammonium iodide is more active on ileum than on atria. 3 There was no striking difference between estimates of affinity based on the effects of agonists on atrial size and the effects on atrial rate nor was there any striking difference between the affinities measured with the different agonists. 4 With the isomers of hyoscyamine there was no striking difference between the affinity for receptors in atria and those in ileum, which is consistent with the low selectivity reported for atropine (racemic hyoscyamine). (-)-S-Hyoscine methiodide had greater affinity for muscarinic receptors in ileum than for those in atria, though the difference is smaller than has been previously observed. (+ )-R-Hyoscine methiodide had no detectable selectivity. The phenomenon of selectivity cannot be wholly ascribed to differences in physicochemical properties of the antagonists: the three-dimensional structures with which the antagonists interact cannot be identical.

Subclassification of atrial and intestinal muscarinic receptors of the rat—direct binding studies with agonists and antagonists

“…The isolated finding of acetylcholine selectivity (5 fold) for inotropic responses (Chassaing et al, 1984) which, however, could not be confirmed by Clague et al (1985) and Barlow & Weston-Smith (1985) thus finds no support in binding studies. In physiological in vitro experiments, ethoxyethyl trimethylammonium iodide (EOE) has been found to be 2 to 4 times more active on ileum than on atria (Barlow & Dawson, 1986;Barlow & Weston-Smith, 1985). In the present binding studies, EOE showed similar affinities for both atria and small intestine.…”

Treatment of Pyridostigmine‐Induced AV Block with Hyoscyamine in a Patient with Myasthenia Gravis

“…Hyoscyamine is the naturally occurring l‐enantiomer, whereas atropine is racemic d,l‐hyoscyamine. Both atropine and hyoscyamine block muscarinic receptors located in the heart and the gut 13 . In clinical practice, hyoscyamine is commonly used to counteract the gastrointestinal side effects of cholinesterase inhibitors given to patients with myasthenia gravis 2 .…”

“…Both atropine and hyoscyamine block muscarinic receptors located in the heart and the gut. 13 In clinical practice, hyoscyamine is commonly used to counteract the gastrointestinal side effects of cholinesterase inhibitors given to patients with myasthenia gravis. 2 In the current patient, hyoscyamine completely abolished episodes of high-grade AV block.…”