In vitro characterization of a novel, potent and selective M3 antagonist.
The pharmacological profile of the competitive muscarinic antagonist (2S, 3'R) 3-quinuclidinyl tropate, abbreviated (-)-2a, was evaluated on rabbit vas deferens (M1/M4-like; pA2=9.10), guinea-pig left atrium (M2; pA2=9.30), guinea-pig ileum (M3; pA2=10.33) and guinea-pig uterus (M4 putative; pA2=9.70) muscarinic receptors and on the five subtypes of muscarinic receptors expressed individually in CHO-K1 cells. The drug shows an affinity for the M3 receptor subtype at least 10-fold higher than 4-DAMP, p-HHSiD and zamifenacin, used as reference drugs. These results suggest (-)-2a as a novel, potent and selective M3 antagonist that may have therapeutic potential in the treatment of conditions associated with increased smooth muscle contractility.
Ghelardini
C
C
Department of Preclinical and Clinical Pharmacology, Florence, Italy.
Bartolini
A
A
Galeotti
N
N
Bellucci
C
C
Dei
S
S
Gualtieri
F
F
D000818:Animals; D016275:Atrial Function; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology*; D011812:Quinuclidines / Q000494:pharmacology*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014590:Uterine Contraction / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic; C094864:3-quinuclidinyl tropate