CHARACTERIZATION OF THE PHYSICOCHEMICAL PROPERTIES OF THE IMIDAZOPYRIDINE DERIVATIVE ALPIDEM - COMPARISON WITH ZOLPIDEM

Zolpidem and Alpidem are 2 new imidazopyridine derivatives that repres ent a novel chemical and therapeutic class in the treatment of sleep a nd anxiety disorders, respectively. The former is a hypnotic agent and the latter behaves as an anxiolytic drug. In contrast to the benzodia zepines, both compounds act selectively at the omega1 (BZ1) but not at the omega2 (BZ2) modulatory sites of the GABA(A) supramolecular compl ex. The lack of affinity for omega2 (BZ2) modulatory sites may account for the absence of myorelaxant effects of these drugs. In order to de termine the parameters that are important for the mode of interaction of these compounds with omega1, modulatory sites, their physico-chemic al properties have been characterized and compared. Focus is directed on crystalline structures obtained from X-ray analysis, and electronic properties as electrostatic potential maps, atomic charges, delocaliz ation effects, and electron densities obtained by ab initio molecular orbital calculations.