S-(-)-ET 126: a potent and selective M1 antagonist in vitro and in vivo

The pharmacological profile of the competitive muscarinic antagonist S-(-)-alpha-(hydroxymethyl)benzeneacetic acid 1-methyl-4-piperidinyl ester (S-(-)-ET 126) was evaluated on M1 (rabbit vas deferens; pA2=8.99), M2 (rat left atrium; pA2=8.21) and M3 (rat ileum; pA2=6.84) muscarinic receptors in comparison with pirenzepine. The drug shows a subtype selectivity (M1/M2=8; M1/M3=178; M2/M3=22) that proposes it as a useful pharmacological tool for receptor studies. S-(-)-ET 126, like pirenzepine, prevents the antinociception induced by M1 agonists (McN-A-343 and AF-102B). Unlike pirenzepine and spirotramine, the compound is able to cross the blood brain barrier which makes it useful for in vivo investigations.