Binding profile of the selective muscarinic receptor antagonist tripitramine.
The binding selectivity of the muscarinic antagonist tripitramine has been tested on the five cloned human muscarinic receptor subtypes (Hm1 to Hm5) expressed in chinese hamster ovary (CHO-K1) cells. The results indicate that tripitramine binds to the muscarinic Hm2 receptor with a Ki value of 0.27 +/- 0.02 nM. Tripitramine distinguishes Hm2 vs. Hm4 by a factor of 24 and vs. Hm3 and Hm5 by a factor of 142 and 125, respectively. A lower affinity ratio, about 6-fold, was found between muscarinic Hm2 and Hm1 receptors. A comparative study with the well-known selective muscarinic M2 receptor antagonist methoctramine indicates that tripitramine has gained both potency and selectivity for the muscarinic Hm2 receptor subtype.
Maggio
R
R
Institute of Pharmacology School of Medicine, University of Pisa, Italy.
Barbier
P
P
Bolognesi
M L
ML
Minarini
A
A
Tedeschi
D
D
Melchiorre
C
C
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D003959:Diamines / Q000378:metabolism; D006801:Humans; D008024:Ligands; D018727:Muscarinic Antagonists; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000493:pharmacokinetics; D013816:Thermodynamics
D018076:DNA, Complementary; D003959:Diamines; D008024:Ligands; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D001569:Benzodiazepines; C084480:tripitramine; C054938:methoctramine; D019832:N-Methylscopolamine