Cappelli Andrea, Gallelli Andrea, Braile Carlo, Anzini Maurizio, Vomero Salvatore, Mennuni Laura, Makovec Francesco, Menziani M Cristina, De Benedetti Pier G, Donati Alessandro, Giorgi Gianluca
Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via A. Moro, 53100 Siena, Italy.
Bioorg Med Chem. 2002 Aug;10(8):2681-91. doi: 10.1016/s0968-0896(02)00093-7.
The results of a comprehensive structure-affinity relationship study on the effect of the quaternization (i.e., N-methylation) of structurally different ligands in the classes of tropane and quinuclidine derivatives are described. This study shows that the effects of the quaternization of the basic nitrogen of these 5-HT(3) receptor ligands appear to be strictly structure-dependent suggesting that different binding modes are operative at 5-HT(3) receptor binding site. The different effect of the quaternization of the basic nitrogen of structurally different ligands were rationalized in terms of the interaction with the receptor by means of the combined use of experimental techniques (X-ray diffraction and NMR studies) and computational simulation studies.
