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.
Ghelardini
C
C
Department of Preclinical and Clinical Pharmacology, Florence, Italy.
Bartolini
A
A
Galeotti
N
N
Teodori
E
E
Gualtieri
F
F
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010648:Phenylacetates / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D014649:Vas Deferens / Q000187:drug effects*
C098725:ET 126; D018727:Muscarinic Antagonists; D010648:Phenylacetates; D010880:Piperidines; D010890:Pirenzepine; D002217:Carbachol; D000109:Acetylcholine