Treatment of Alzheimers disease

There are no effective therapies for Alzheimer s disease and no cure. Treatment aims to enhance cholinergic transmission. The most useful drugs are central acetylcholinesterase inhibitors, for example donepezil. Acetylcholinesterase is the enzyme that normally breaks down acetylcholine after it has interacted with its receptors at the synapse. Inhibition of this enzyme in the brain increases the amount of acetylcholine available and prolongs its action. These drugs produce a modest improvement in memory or slow progression of symptoms in some patients. The response to anti-cholinesterase drugs may take several weeks. Their use is limited by side effects, which can be severe. 

Side effects of acetylcholinesterase inhibitors include abdominal cramps, nausea, vomiting and diarrhoea and liver damage. 

Acetylcholine precursors such as lecithin have been tried, but are of limited effectiveness. 

Glutamate acts on A-methyl-o-aspartate (NMDA) receptors in the brain. Drugs have been developed to block these receptors. An example is memantine. 

There are many disorders of the CNS. Psychiatric disorders include types of depression, psychosis and anxiety. Neurological disorders include Parkinson s disease, epilepsy and 

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FK-960 was initially developed for treatment of Alzheimer disease, but it has been abandoned for this indication. However, it is still under clinical trials for therapy of cognition disorders related to schizophrenia. 

HCT-1026 (nitwflurbipwfen) is a nitric oxide-donating derivative of the NSAID flurbiprofen. It is undergoing Phase 1 clinical evaluation for the treatment of Alzheimer disease, but it is more advanced (Phase 11) for overactive bladder and osteoporosis. 

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Current drugs approved for the treatment of Alzheimers disease in the United States have the common mechanism of action being ... 

CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Bruce E. Maryanoff and Cynthia A. Maryanoff. Computer Assisted Molecular Design Related to the Protein Kinase C Receptor, Paul A. Wenderand Cynthia M. Cribbs. Chemistry and Biology of the Immunosuppressant (-)-FK-506, Ichiro Shinkai and Nolan H. Sigal. The Development of Ketorolac Impact on Pyrrole Chemistry and on Pain Therapy, Joseph M. Muchowski. Application of Silicon Chemistry in the Corticosteroid Field, Douglas A. Livingston. Hu-perzine A-A Possible Lead Structure in the Treatment of Alzheimers Disease, Alan P. Kozikowski, X.C, Tang and Israel Hanin. Mechanism-Based-Dual-Action Cephalosporins, Harry A. Albrecht and James G. Christenson. Some Thoughts on Enzyme Inhibitors and the Quiescent Affinity Label Concept, Mien Krantz Index. 

Zimmermann, M. Colciaghi, F Cattabeni, R Di Luca, M. Ginkgo biloba extract from molecular mechanisms to the treatment of Alzheimers disease. Cell. Mol. Biol., 2002, 48 613-623. 

Ali SK, Hamed AR, Soltan MM, Hegazy UM, Elgorashi EE, El-Garf IA et al (2013) In-vitro evaluation of selected Egyptian traditional herbal medicines for treatment of alzheimer disease. BMC Complement Altern Med 13 121... 

The design of bifunctional AChE inhibitors was achieved in order to obtain potent and selective derivatives. Tacrine, an AChE inhibitor used for the treatment of Alzheimer disease (AD) patients, has been dimerized leading to the bis- 3Lcnnt derivative (Eigure 18.17). The length of the methylene chain was optimized in order to obtain a potent and selective homodimer. ilA-tetrahydroaminacrine... 

Forsythe E. and Ritzline P. D. (1998) An overview of the etiology, diagnosis, and treatment of Alzheimer Disease. Phys Ther 78(12), 1325-1331. 

Solomon B. (2007) Beta-amyloid based immunotherapy as a treatment of Alzheimers disease. Drugs Today (Bare), 43 333-42. 

Churcher, L Simpson, P. B. Nanthakumar, C. B. Method for identifying modulators of y-secretase or notch for treatment of Alzheimers disease, multiple sclerosis, and cancer. PCT Int. Appl. WO... 

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