ATROPINE AND GLYCOPYRRONIUM SHOW SIMILAR BINDING PATTERNS TO M(2) (CARDIAC) AND M(3) (SUBMANDIBULAR-GLAND) MUSCARINIC RECEPTOR SUBTYPES IN THE RAT

Atropine and glycopyrronium are frequently used for premedication to reduce oral and respiratory secretions and prevent bradycardia. Glycopyrronium is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this investigation was to possible selectivity of glycopyrronium for M(2) and M(3) muscarinic receptor subtypes. Muscarinic receptor subtypes in Wistar rat ventricle and submandibular gland homogenates characterized with [H-3]-N-methylscopolamine ([H-3]-NMS) by ligand binding studies. Inhibition of [H-3]-NMS binding by non-labelled compounds showed the following order: in rat ventricle: glycopyrronium > atropine much greater than otenzepad > hexahydrosiladiphenidol (HHSiD) > pirenzepine; in rat submandibular gland: glycopyrronium > atropine much greater than HHSiD much greater than pirenzepine > otenzepad. These were similar to the expected order of frequency of M(2) and M(3) subtypes, respectively. Glycopyrronium showed similarly high affinities for both M(2) (K-i = 1.889 (SEM 0.049) nmol litre(-1)) and M(3) (K-i = 1.686 (0.184) nmol litre(-1)) subtypes. Glycopyrronium bound to a homogeneous population of binding sites in both tissues and showed no selectivity for M(2) or M(3) muscarinic receptor subtypes.