Donepezil hydrochloride for Dementia Related to Alzheimer's Disease...

We know that, ARICEPT® [donepezil hydrochloride, see structure  (source-chemSpider) ] is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (±)-2,3-dihydro-5,6-dimethoxy-2 -[[1-(phenylmethyl)-4-piperidinyl]- methyl]-1H-inden-1-one hydrochloride. Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020.

Acetylcholinesterase is the target of many Alzheimer's Dementia drugs , nerve gases, particularly the organophosphates (e.g. Sarin) and insecticides (e.g. carbaryl). These agents — known as cholinesterase inhibitors — block the function of acetylcholinesterase and thus cause excessive acetylcholine to accumulate in the synaptic cleft. The excess acetylcholine causes neuromuscular paralysis (i.e. interminable muscle contractions) throughout the entire body, leading to death by asphyxiation.

The U.S. Food and Drug Administration approved the first generic versions of Aricept (donepezil hydrochloride) orally disintegrating tablets on Dec. 11. Donepezil hydrochloride is indicated for the treatment of dementia related to Alzheimer's disease. Orally disintegrating tablets dissolve on the tongue, without having to be swallowed whole. This may make it easier to take the medication for older or disabled patients who have difficulty swallowing.

Alzheimer's disease :

Alzheimer's disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks of daily living. In most people with Alzheimer's disease, symptoms first appear after age 60. Alzheimer's disease is the most common cause of dementia among older people, but it is not a normal part of aging...

Ref : http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm194173.htm

Quetiapine fumarate (Seroquel XR) for Major Depressive Disorder (MDD)....

Quetiapine fumarate (see structure) is marketed by AstraZeneca as Seroquel or SeroquelXR and by Orion Pharma as Ketipinor, is an atypical antipsychotic schizophrenia used in the management of, bipolar I mania, bipolar II depression, bipolar I depression, and used off-label for a variety of other purposes, including insomnia and anxiety disorders.

It is sometimes used off-label, often as an augmentation agent, to treat such conditions as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression, Tourette syndrome, and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.

Astra-Zeneca, recently  announced that the FDA has approved once-daily Seroquel XR (quetiapine fumarate) Extended Release Tablets as adjunctive (add-on) treatment to antidepressants in adults with Major Depressive Disorder (MDD). Seroquel XR is the only medication in its class approved by the FDA to treat both major depressive disorder as adjunctive therapy and acute depressive episodes associated with bipolar disorder as monotherapy. The company claims that this approval for Seroquel XR provides physicians with a new adjunctive treatment option for patients with MDD who have an inadequate response to their current antidepressant. FDAs approval of Seroquel XR is based on a clinical development program in MDD involving 939 patients randomized across two studies that assessed the efficacy and safety of once-daily treatment with Seroquel XR as adjunctive treatment to antidepressants.....

Ref : http://www.astrazeneca.com/media/latest-press-releases/2009/seroquel-us-MDD?itemId=7660757

Dabigatran etexilate a better drug than warfarin for VTE?.

We know that Dabigatran is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and may replace warfarin as the preferred anticoagulant in many cases. It is orally administered as the prodrug dabigatran etexilate (marketed as Pradaxa since April 2008 in European countries and Pradax in Canada). It was developed by the pharmaceutical company Boehringer Ingelheim.

Now researchers lead by  Dr. Sam Schulman, a professor of medicine of the Michael G. DeGroote School of Medicine (McMaster University), who conducted a randomized, double-blind trial of 2,539 patients with acute VTE (venous thromboembolism) have found that dabigatran (see structure) is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner. 

As per the claim by the researchers, the improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4 percent of the dabigatran etexilate group (30 patients) and 2.1 percent of the warfarin group (27 patients) experienced recurrent VTE. The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 205 patients experienced bleeding (including 20 patients with major bleeding) versus 277 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups. Hope patients suffering from VTE will now breathe a sigh of relief....

Ref : http://dailynews.mcmaster.ca/story.cfm?id=6511

Engineered tobacco plants have more potential as a biofuel

Engineered tobacco plants have more potential as a biofuel

New RNA interference technique can silence up to five genes

New RNA interference technique can silence up to five genes

Nonanal (odour produced in humans and birds) - an attractant for the Culex mosquito ?

In continuation of my update on developments in mosquito repellents,  I  found this  interesting info. In  my earlier blog, I mentioned that carbon dioxide   emitted in human  breath  is  the main  attractant  for the    Culex mosquito to find people, aiding the transmission of these deadly diseases. Now scientists from University of California, Davis, have identified the dominant odor naturally produced in humans and birds that attracts the blood-feeding Culex mosquitoes, which transmit West Nile virus and other life-threatening diseases. As per the claim by the researchers, Nonanal (nonanaldehyde or pelargonaldehyde see below structure) is the powerful semiochemical that triggers the mosquitoes' keen sense of smell, directing them toward a blood meal. A semiochemical is a chemical substance or mixture that carries a message.The antennae of the Culex quinquefasciatus are highly developed to detect even extremely low concentrations of nonanal. Mosquitoes detect smells with the olfactory receptor neurons of their antennae.

The UC Davis researchers tested hundreds of naturally occurring compounds emitted by people and birds. They collected chemical odors from 16 adult human subjects, representing multiple races and ethnic groups. More interestingly, Leal and Syed found that nonanal acts synergistically with carbon dioxide, a known mosquito attractant.  Nonanal, in combination with carbon dioxide, increased trap captures by more than 50 percent, compared to traps baited with carbon dioxide alone. Hope this discovery will help those searching for cheaper, environment friendly  repellents.

Ref : http://www.news.ucdavis.edu/search/news_detail.lasso?id=9289 

Oleanolic acid capsules for Hepatitis B......

We  know that Oleanolic acid is a naturally occurring triterpenoid, widely  distributed in food and medicinal plants, related to betulinic acid. It can be found in Phytolacca americana (American pokeweed), and Syzygium spp, garlic, etc. It is relatively non-toxic, antitumor, and hepatoprotective (antihepatotoxic - protecting liver cells against toxins) as well as exhibiting antiviral properties.

Oleanolic acid was found to exhibit strong anti-HIV activity, the related compound betulinic acid was used to create the first commercial maturation inhibitor drug. It was first studied and isolated from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phordendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). Other Syzygium species including java apple (Syzygium samarangense) and rose apples contain it.

Now Biostar Pharmaceuticals, Inc. has completed preparation to launch its flagship Xin Aoxing Oleanolic Acid ("Xin Aoxing") Capsules for the treatment of Hepatitis B in Beijing and Shanghai in early January 2010.....

Ref : http://www.biostarpharmaceuticals.com/newsdisp.asp?id=78

Happy New Year 2010

Wishing one and all a happy, prosperous and peaceful new year 2010...

Dr.Umesh




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Combination of Phentermine & Topiramate for obesity treatment......

We know that Phentermine (see structure) is  an appetite suppressant of the  amphetamine and phenethylamine class. It is approved as an appetite suppressant to help reduce weight in obese patients. Its  usually used for short-term and in combination with exercise, diet and behavioral modification. Is typically prescribed for individuals, who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.  

Mode of action : Phentermine, in doses clinically used, works on the hypothalamus portion of the brain to release norepinephrine, a neurotransmitter or chemical messenger that signals a fight-or-flight response, reducing hunger. Phentermine works outside the brain as well to release epinephrine or adrenaline causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction. At high doses, phentermine releases serotonin and dopamine as well, but such doses are never used in clinical medicine.  

Topiramate (structure below), is a known anticonvulsant agent and  also  reported  for  the  treatment   of

SSRI-  induced weight gain in anxiety disorders. However a combination   of these two drugs (Phentermine & Topiramate) has been  tried by VIVUS, Inc. and has submitted New Drug Application (NDA)   to the U.S. Food and Drug Administration (FDA) seeking approval of Qnexa (Phentermine & Topiramate combination) - its investigational drug for the treatment of obesity, including weight loss and maintenance of weight loss, in patients who are obese or overweight with co-morbidities such as hypertension, type 2 diabetes, dyslipidemia or central adiposity.

The NDA submission follows the successful completion of the phase 3 program for Qnexa, including the recently announced results from the two pivotal, year-long phase 3 studies (EQUIP and CONQUER). In these trials, patients treated with all three doses of Qnexa achieved significant percent and categorical weight loss compared to placebo and met regulatory requirements for weight loss products as defined in the current FDA Guidance for Developing Products for Weight Management. Patients treated with Qnexa also had significant dose-related improvements in a variety of secondary endpoints including reductions in cardiovascular and metabolic risk factors. Hope people with obesity, will breathe a sigh of relief in the near future....

Ref : http://ir.vivus.com/releasedetail.cfm?ReleaseID=433172

Gren tea for new type of H1N1 Flu ......

In continuatation of my update on Epigallocatechin gallate (EGCg), I find this info something different and interesting too. We are aware about the antioxidant and anticancer activities of this compound, but now researchers from Central Research Institute of ITO EN, Ltd., & School of Pharmaceutical Sciences, University of Shizuoka have found the same compound to inhibits flu infection. As per the researchers claim, the compound had an inhibitory effect against three types of influenza viruses, including the swine-origin H1N1 virus that caused pandemic flu in 2009, and that its effect did not depend on the type of virus. These findings once again suggest that green tea is effective in preventing flu.

Gargling with green tea has already proved to prevent the onset of seasonal flu. It has become clear that catechin, a major type of polyphenol in green tea, plays a major role in prevention of flu infection, and that, among different types of catechin, EGCg displays the strongest antiviral activity. More interestingly, the researchers have conducted examinations to see if EGCg also shows antiviral activity against the new type of H1N1 virus, regardless of viral subtypes.

Solutions containing three types of viruses including the H1N1 virus were mixed with EGCg extracted from green tea. The mixture was added to cultured cells, which were thus infected. The cells were incubated for a set period of time, and the number of infected cells was counted. The concentration of EGCg at which virus infection was inhibited to 50% of the level of infection without EGCg was calculated.

The experiments showed that EGCg prevented flu virus infections at lower concentrations than Amantadine (a drug used to prevent and treat flu). A typical concentration of EGCg in green tea infused from a teapot is reported as 5,000-7,000 micromoles/L. Therefore, these results indicate that green tea diluted 1,000-fold or more is effective to halve infections by three types of viruses, including H1N1.

Those interested to know the details about green tea can visit the site.

Ref : http://www.itoen.co.jp/eng/corporate_info/index.html