Stereoselective interaction of uncharged esters at four muscarinic receptor subtypes

Muscarinic receptor binding activity of polyoxygenated flavones from Melicope subunifoliolata

“…The methylenedioxyphenyl groups of the methoxyflavones, however, resemble part of the structures of darifenacin (M3 antagonist) and zamifenacin (M3 antagonist) (Broadley and Kelly, 2001). Although methoxyflavones lack nitrogen, a few uncharged competitive antagonists, namely, ''carbo" analogues, have been described previously (Barlow and Tubby, 1974;Waelbroeck et al, 1996). Furthermore, it has been reported recently that the presence of nitrogen is not essential for the allosteric actions of the steroidal analogues of WIN 51,708 and WIN 62,577 (Lazareno et al, 2002).…”

Analogs of WIN 62,577 Define a Second Allosteric Site on Muscarinic Receptors

“…This finding is reminiscent of the simultaneous binding of 2,4-diaminopyrimidine and p-aminobenzoyl-glutamate (subcomponent moieties of methotrexate) to dihydrofolate reductase and their allosteric interactions with coenzyme analogs (Birdsall et al, 1978(Birdsall et al, , 1980. It has generally been assumed that muscarinic ligands that bind to the primary or, especially, allosteric site should have a basic nitrogen, although a few uncharged competitive antagonists ('carbo' analogs) have been described previously (Barlow and Tubby, 1974;Waelbroeck et al, 1996). The allosteric actions of the steroids, 10 and 11, mean that this requirement is not essential.…”

A Qualitative Model for the Histamine H3 Receptor Explaining Agonistic and Antagonistic Activity Simultaneously

“…It has been shown that an ionic bond between protonated ligands and GPCRs facilitates, but is not essential for receptor binding. E.g., cationic agonists and cationic antagonists of muscarinic acetylcholine receptors form an ionic bond with the Asp in TMIII, and equally potent but uncharged muscarinic antagonists recognize the same binding site without interacting with this Asp [24,25] .…”