Role of muscarinic antagonist methacine metabolites in regulation of inflammation

Abstract

It is known, that synthetic muscarinic antagonists ipratropium bromide, trospium chloride, oxybutynin chloride form pharmacologically inactive metabolites and have slight side effects compared with muscarinic antagonists, which metabolites possess pharmacological activity. On the model of the quaternary muscarinic antagonist methacine we revealed that this drug undergoes hydrolysis at the ester bond to yield pharmacologically inactive 2-hydroxy-2,2-diphenylacetic acid and pharmacologically active muscarinic/nicotinic cholinoceptor agonist choline. Long-term course administration of methacine increases its antimuscarinic effects, connected with side effects extension. However single administration of methacine with cholinesterase inhibitor is an effective procedure to pathochemical stage of anaphylactic shock prevention. Methacine-induced immune response (non-neuronal effects) limits stress ulcer formation under water immersion stress influence. Obtained data may be significant for mechanism of new muscarinic antagonists action understanding and for scope evaluation of drug metabolites activity therapeutic application.

Keywords

muscarinic antagonist methacine / muscarinic and nicotinic agonist choline / anaphylactic shock / water immersion stress / B-lymphocytes

RIGHTS & PERMISSIONS

Sapronoѵ N.S., Nezhinskaya G.I., Vladykin A.L.