Description
Dimebon Development
In 1969 Alexey Kost synthesized a molecule, later called Dimebon, in his laboratory at the chemistry faculty of the Moscow State University. In 1983 Dimebon was first produced as an anti-allergic agent by Novokuznetsk corporation "Organika", however, due to a lack of financing and a growing popularity of foreign preparations like Claritin and Suprastin Dimebon was driven out of the market. The last consignments of the preparation were produced by the open-joint-stock company "Organika" in 1997. At this, the history of Dimebon could have stopped, if experts of IPAC RAS (Institute of Physiologically Active Compounds of Russian Academy of Sciences) in the scientific town Chernogolovka, Russia, didn't pay attention to it. At the beginning of 1990th years IPAC began to search for substances able to protect human nervous system. After having tested thousands of chemical compounds, scientists stopped at the group of so called gamma-carbolines. While checking which of them had been already used in the medical practice, they came across Dimebon as it also referred to gamma-carbolines. "We chose Dimebon for a high efficiency, by the way it had already been approved by the Ministry of Health what allowed to reduce clinical trials", - explained Sergey Batchurin, CEO of IPAC.
Mechanism of Dimebon action
Dimebon is a blocker of H1-receptors. It operates through multiple mechanisms of action, both blocking the action of neurotoxic beta-amyloid proteins and inhibiting L-type calcium channels, modulating the action of AMPA and NMDA glutamate receptors, and may exert a neuroprotective effect by blocking a novel target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. It also blocks a number of other receptors including alpha-Adrenergic receptors and the serotonin receptor subtypes 5-HT2C,5-HT5A and 5-HT6 Dimebon efficiency was first checked in vitro, then in vivo (on rats). Batchurin made a canny move. Avoiding expenses on clinical trials of a new effect of Dimebon on people, he arranged with Moscow mental hospital named after P.B.Gannushkin so that doctors should give Dimebon to patients suffering both from allergy and Alzheimer`s Disease (a total of 14 people). Officially they were treated from allergy and their memory imrovements were observed therewith. The results appeared to be promising, and 10 scientists of those participating in the research headed by Sergey Batchurin immediately filed their own patent application for a new method of treatment of Alzheimer`s Disease. But there was an acute need in a foreign investor for financing official clinical trials and receipt of international patents. Results of scientific research studies.
At the end of 2005 Medivation company began official clinical trials of Dimebon as a drug for Alzheimer`s Disease The research was conducted on 180 patients in 11 Russian clinics. The relsults appeared to be sensational: Dimebon didn't just suspend the development of Alzheimer`s Disease, but also reversed it, contributing to reconstruction of the broken links in the cerebrum. Patients with mild to moderate Alzheimer's disease who were taking Dimebon, showed benefit in five critical areas: memory, thinking, the ability to carry out activities of daily living like eating or dressing, behavior, and overall function. Improvements were noted at six months and continued until the end of the 12-month, Phase 2 study, which was conducted in Russia. By the end of the mid-stage trial, patients treated with Dimebon had not gotten any worse and scored higher on thinking and memory tests, while those taking a placebo continued to deteriorate.
In the current study, the authors noted that Dimebon is the first drug for Alzheimer's disease that continued to produce improvement in patients over a 12-month period. Other approved drugs for Alzheimer's, like Aricept, Exelon, Namenda and Razadyne, do not have this sustained effect, though researchers suggest that these drugs may slow progression of the disease over many years. Researchers believe the medication works by stabilizing mitochondria, which act like tiny batteries to generate energy within the cell. The drug may also act by inhibiting the death of brain cells. In the current trial, the drug appeared to be safe. Nearly one in five participants taking Dimebon complained of occasional dry mouth, and some patients on the drug reported feeling depressed. But no one opted out of the study because of the side effects.
Besides, Pfizer, Medivation and IPAC found out, that Dimebon also helps from one more disease, destructing the cerebrum - Huntington's chorea. This disease is found in 1000 times more rarely than Alzheimer`s Disease, but there are no drugs from it yet at all.
The interest to a new drug from Alzheimer`s Disease is so great in USA, that Americans persist to phone to "Organika" factory in Novokuznetsk, in order to get to know if they can buy Dimebon in private capacity.
In 2005 Medivation placed 5,6 mln shares on change at the price $2 per share for conducting official clinical trials of Dimebon as a drug for Alzheimer`s Disease on this money. Later, the cost of Medivation shares first flew up to $12 per share, and by June, 2007, when an annual cycle of clinical trials finished, - they grew up to $20 per share. Now Medivation proceeded with Phase III of clinical trials and in case of successful completeness, the preparation could be sold in the biggest market - in USA.
Sources:
1.SalynnBoyles, WebMD Health News. Alzheimer's Drug Nothing to Sneeze At. - http://www.medicinenet.com/script/main/art.asp?articlekey=88822
2.Grigor`ev V.V. Autoreport of the dissertation. Development of the search system of preparations for correction of disorders of cognitive functions during neurodegenerative diseases in the series of ligands for glutamate receptors, - Moscow 2009.
3.Kutuzov Roman. Dimebon. To remember all, - Forbes. March 2009, P. 121-122.
4. Dimebon. - http://ru.wikipedia.org/wiki/Димебон
5.Dimebon. - http://en.wikipedia.org/wiki/Dimebolin