Multi-Target-Directed Ligands To Combat Neurodegenerative Diseases

Abstract

In Table 1, the word "Trihexyphenidyl" is misspelled and the structures given for L-dopa and Piribedil are incorrect. The correct structures for these compounds are shown below.

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

“…During the last few decades, the concept of multi-target drug activity has been proposed (Wong et al, 2008;Cavalli et al, 2008;Combarros et al, 2009). According to this concept, the mechanisms responsible for the beneficial actions of drugs can be realised via multiple actions of the compound on a number of receptors; in this case, effective changes in the concentrations of neurotransmitters may be much lower than if only one receptor signaling system underlies the drug's activity.…”

“…Thus, it can be speculated that, in the mouse test battery employed in this study, dimebon affects a number of receptors and may act as a multi-target drug, i.e. the concentrations used in this study, which correspond to sub-threshold levels for receptor activation via a mono-target mechanism, are only able to evoke physiological effects by synergistic activation of several neurotransmitter systems (Youdim and Buccafusco, 2005;Cavalli et al, 2008). The memory-enhancing effects of dimebon may indicate simultaneous activity toward AMPA, NMDA, dopamine and serotonin receptors, all of which have been involved in inhibitory and appetitive hippocampus-dependent learning (Ungerer et al, 1998;Orsetti et al, 2001;Rogawski and Wenk, 2003;LaLumiere et al, 2003;Lynch and Gall, 2006;Balschun et al, 2006;Da Silva Costa et al, 2009;Benchenane et al, 2010).…”

Biological Activity of sym-Triazines with Acetylcholine-like Substitutions as Multitarget Modulators of Alzheimer’s Disease

“…9,10 However, disease progression in AD is multifactorial in nature, and hence, targeted inhibition of a single disease pathology is compensated by concurrent deleterious pathways. 11,12 Combination therapies, which implement numerous drug entities to target multiple pathologies simultaneously, have thus emerged as strong candidates for the development of effective disease-modifying strategies. 12 In view of the above, complications associated with the administration of multiple single-target drug entities such as conflicting bioavailabilities, pharmacokinetics, and metabolism may be circumvented through the implementation of multitarget therapies.…”

Chlorophenols in organic synthesis

“…Moreover nitrogencontaining organic compounds possess diverse biological activity, but also they could be a building blocks for various macromolecules and new materials [31][32][33][34].…”

“…Причем азотсо-держащие органические соединения не только обладают разнообразной био-логической активностью, но и служат в качестве строительного блока для различных макромолекул и новых ма-териалов [31][32][33][34].…”