METHYLENE BLUE 2008 clinical trial results

This is an unprecedented result in the treatment of Alzheimer's disease. We have demonstrated for the first time that it may possible to arrest the progression of this disease by targeting the tangles which are highly correlated with the disease. Claude M. Wischik CEO, TauRx Pharmaceutical
[5]

The University of Aberdeen held a Phase IIb clinical trial[6][5] on 321 people with mild Alzheimer's disease in the United Kingdom and Singapore and found that taking the drug 3 times a day over a period of 50 weeks slows down the development of Alzheimer's disease by about 81%. [7] The patients were split into four groups: one group taking a dose of 30mg, another taking a dose of 60mg, a third taking a dose of 100mg and the fourth taking a placebo. The 60mg dosage gave the best results, giving an 81% reduction in mental degression compared to those on the placebo. Only those on the placebo experienced a decline in mental function. A larger Phase 3 trial is planned for 2009 with an idea to see whether Rember can prevent the formation of the disease in the first place.[3] TauRx are also looking into starting a trial of the drug on patients suffering from Parkinson's disease; as Rember also has effects on the synuclein fibres in the brain.[8] If the results of the two trials correlate then it is anticipated that the drug could be on the market by 2012.[5] Debate began soon after the announcement over the funding of the drug under the UK's National Health Service [9] The initial press release from TauRx has been characterized as "very aggressively worded".[10] A lengthy article at the Alzheimer Research Forum provoked further comments.[11]

Diazoxide
A drug currently used to treat hypoglycemia, and once commonly prescribed in the 1970s and 80s to help with hypertension, may have a new use: treating Alzheimers patients. Researchers at the National Institute on Aging (NIA) have found that the drug, diazoxide, improves memory and learning in mice engineered to have Alzheimers. Scientists discovered that the drug stabilizes nerve cells in the brain and prevents their destruction, a common occurrence under Alzheimers conditions. Diazoxide also enhances blood flow through the brain and keeps under control the two proteins beta-amyloid and tau, whose buildup in the brain is considered a hallmark of the disease. These intriguing findings open new avenues of basic research that may increase our understanding of how modulating the electrical activity of nerve cells may slow the damage wrought by Alzheimers disease pathology, said NIA Director Richard J. Hodes, M.D.

More research will be needed before we can determine whether this may be a potential therapy for Alzheimers. For the study, NIA scientists analyzed two groups of Alzheimers mice: one group was given diazoxide in drinking water and the other was given a placebo. Once eight months had passed, the diazoxide mice performed better than the placebo group in a learning and memory test. The brain tissue of the diazoxide mice revealed that the drug may have hindered toxic cellular changes common in Alzheimers disease, with fewer deposits of the dangerous proteins, less oxidative stress damage, and better blood flow. To better understand the complex biological mechanisms by which diazoxide may exert a positive effect on nerve cells, we then studied the effects of diazoxide on cultured nerve cells, said Mark P. Mattson, Ph.D., chief of NIAs Laboratory of Neurosciences in Baltimore. The study shows that diazoxide also triggers and opens cell channels that enable the flow of potassium, which in turn calms electrical nerve cell activity in areas of the brain associated with learning and memory. It also lowers excessive calcium, often found in nerve cells in brains affected by Alzheimers. Importantly, these benefits occurred with a dose of diazoxide low enough to avoid producing a significant decrease in blood pressure, Mattson noted. The study can be found in the Nov. 15, 2010, print edition of the Journal of Alzheimers Disease. Diazoxide is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. This switches off voltage-gated calcium ion channels which inhibits the generation of an action potential. [edit]Uses It is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.[1] It is also used to decrease hypoglycemia due to the secretion of insulin in disease states such as insulinoma (a tumor producing insulin)[2] or congenital hyperinsulinism.

7-chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide 7-chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxi Identi CAS number 364-98-7 ATC code C02DA01 V PubChem CID 3019 IUPHAR ligand ID 2409 DrugBank APRD00914 ChemSpider 2911 UNII O5CB12L4F Chemical Formula C8H7ClN2O Mol. mass 230.672 g/m SMILES eMolecules Pharmacokinetic Protein binding 90% Metabolism Hepatic oxi

Half-life Excretion Pregnancy cat. Legal status Routes

21-45 hour Renal Therapeutic considerat C(AU) C(US POM (UK) Oral, intrav