Alzheimer Disease: Van der Schyf CJ

Geldenhuys WJ, Van der Schyf CJ. · Department of Pharmaceutical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, USA. · Curr Top Med Chem. · Pubmed #18691131 No free full text.

Abstract: Recently, the serotonin 5-HT(6) receptor has been identified as a drug target for attenuating cognitive deficits associated with Alzheimer's disease (AD). Additionally, this receptor may also play a role in schizophrenia, anxiety and obesity. Reports in the literature suggest that the production of selective antagonists for the 5-HT(6) receptor has increased during the last 10 years, with some compounds currently in clinical trials for the treatment of AD. In this review, we will address the rationale for using 5-HT(6) receptor antagonists in AD, as well as report on current advances in the understanding of the structure-activity relationships required to synthesize 5-HT(6) receptor antagonists.

Van der Schyf CJ, Mandel S, Geldenhuys WJ, Amit T, Avramovich Y, Zheng H, Fridkin M, Gal S, Weinreb O, Bar Am O, Sagi Y, Youdim MB. · Department of Pharmaceutical Science, Northwestern Ohio Universities College of Pharmacy, Rootstown, OH 44272, USA. · Curr Alzheimer Res. · Pubmed #18220515 No free full text.

Abstract: Traditionally, drug design programs are focused on optimizing the specificity of lead compounds against a carefully selected drug target. Disappointingly, this approach to discover a "magic bullet" drug has not met with the expected success for CNS disorders. Transcriptomics and proteomic profiling of neurodegenerative diseases have indicated that they are poly-etiological in origin and that the processes leading to neuronal death are multifactorial. An emerging concept is the design of drug ligands that modulate multiple drug targets identified for a particular disease. In this review we explore some examples of multifunctional drugs which may be useful in the treatment of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.

Geldenhuys WJ, Van der Schyf CJ. · Texas Tech University Health Sciences Center, School of Pharmacy, 1300 Coulter Drive, Amarillo, TX 79106, USA. · Med Hypotheses. · Pubmed #16962723 No free full text.

Abstract: The recently discovered serotonin 5-HT(6) receptor is a novel target for the treatment of cognitive decline associated with neurodegenerative diseases such as Alzheimer's disease (AD). Several studies have shown that antagonism of this receptor leads to improved learning and memory. Two serotonin 5-HT(6) receptor antagonists are currently in Phase II clinical trials for cognitive enhancement. Striking structural similarities between the polycyclic features of some 5-HT(6) antagonists and those of the cis-syn-cis triquinane ring system led us to propose that triquinane-derived compounds may represent a novel class of 5-HT(6) receptor antagonists. Using computational methodologies, we propose a structure with features that may impart potent 5-HT(6) receptor antagonistic activities to the triquinane ring complex. Related compounds, once synthesized, may have possible utility in the treatment of cognitive decline associated with AD.