Combination of COX-2-selective NSAID with PPI can reduce risk of stomach, intestinal ulcers

Non-steroidal anti-inflammatory drugs (NSAIDs)—including ibuprofen, diclofenac, naproxen and others—are commonly used pain medications that are generally safe but may increase the risk of developing stomach and intestinal ulcers.

After researchers analyzed a large number of clinical trials that compared different ways of reducing these risks of NSAIDs, they found that the best strategy with the lowest overall risk was to combine a certain type of NSAID, known as a COX-2-selective NSAID, with a proton pump inhibitor (PPI). PPIs are most often used to treat heartburn and gastro-oesophageal reflux disease.

"The combination of a COX-2-selective NSAID with a PPI will be expensive and is not recommended for all patients who need to be on a NSAID; however, it is the safest and most effective treatment strategy for those at high risk of ulcer bleeding from NSAID treatment," said Prof. Jin Ling Tang, co-author of the Alimentary Pharmacology and Therapeutics study.

Sun Pharma Receives FDA Approval For BromSite (bromfenac ophthalmic solution)

Sun Pharmaceutical Industries Ltd and includes its subsidiaries or associate companies) recently announced that one of its wholly owned subsidiaries has received approval from USFDA for its New Drug Application (NDA) related to BromSite™ (bromfenac ophthalmic solution) 0.075% for the treatment of postoperative inflammation and prevention of ocular pain in patients undergoing cataract surgery. BromSite™ is the first non-steroidal antiinflammatory drug (NSAID) approved by the USFDA to prevent pain and treat inflammation in the eye for patients undergoing cataract surgery; other NSAIDs in this class are currently indicated for the treatment of inflammation and reduction of pain.

BromSite™ developed by InSite Vision, is the first bromfenac ophthalmic solution formulated in DuraSite™, a polymer-based formulation that can be used to improve solubility, absorption, bioavailability, and residence time as compared to conventional topical therapies. Sun Pharma acquired InSite Vision in November 2015 and is likely to commercialize BromSite™ through its newly formed, US-based division, Sun Ophthalmics, in the second half of 2016. As per IMS MAT January 2016, the U.S. NSAID Ophthalmic market grew by 8%, generating approximately US$400mn in sales and about 4 million prescriptions, providing an attractive market for Sun Pharma to participate.

Sun Ophthalmics has crossed a key business milestone through BromSite’s approval. Sun Ophthalmics targets to provide eye care practitioners products that enhance their practice patterns and treatment options and to deliver those products through its unique, concierge level approach to customer care. With BromSite’s approval and additional late-stage candidates in its pipeline, Sun Ophthalmics is strongly positioned to offer a range of beneficial products and establish itself as a respected and trusted partner.

In two multi-center, randomized, placebo-controlled Phase-3 studies, a significantly higher proportion of BromSite treated patients were pain-free at Day 1 post-surgery (77% and 82%) compared to patients treated with vehicle control (48% and 62%) (p<0.001). Additionally, a significantly higher proportion of subjects administered BromSite™ were inflammation-free at day 15 post-cataract surgery (57% and 38%), compared to a vehicle control group (19% and 22%) (p<0.001 and p=0.035).

“Over the years, I’ve worked closely with the InSite team and watched them develop multiple high quality products using the DuraSite platform,” commented Dr. Richard L. Lindstrom, MD, founder and attending surgeon of Minnesota Eye Consultants and Adjunct Professor Emeritus at the University of Minnesota Department of Ophthalmology. “Today, I am pleased to see BromSite™ advance from development to market. I am confident there will be significant clinician interest in this new product. As the first NSAID labeled to prevent pain and reduce inflammation post-cataract surgery, BromSite’s approval is timely and will be welcomed by patients and clinicians alike.”

Sun Pharma Receives FDA Approval For BromSite (bromfenac ophthalmic solution)

Cobiprostone shows promise against NSAID-induced gastric mucosal injury

Cobiprostone shows promise against NSAID-induced gastric mucosal injury: Sucampo Pharmaceuticals, Inc. today announced the presentation of preclinical data at Digestive Disease Week 2012, in San Diego, which demonstrates the protective effect of cobiprostone (see structure)  against epithelial barrier dysfunction in models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric mucosal injury.

Ref : http://investor.sucampo.com/phoenix.zhtml?c=201197&p=irol-newsArticle&ID=1697806&highlight=

Celecoxib reduces the risk of common skin cancer in humans.....

We know that Celecoxib   is a non-steroidal anti-inflammatory drug (NSAID)  used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer. It is known under the brand name Celebrex or Celebra for arthritis and Onsenal for polyps. Celecoxib is available by prescription in capsule form.

Researchers from UC-San Francisco and Children's Hospital Oakland,  (Dr. Tang was was an assistant professor at UC-San Francisco and Children’s Hospital Oakland  when the trial was conducted) have come up with very interesting results for the same drug. The drug can reduce the risk of a common skin cancer in humans. Though celecoxib, is associated with an increased risk of heart attack and stroke in some people, it's possible that topical application could have a safer, protective effect for people prone to developing the cancers, called basal cell carcinomas, the researcher believes.

For the current research, Tang and her colleagues capitalized on a previous finding suggesting that celecoxib, a NSAID, can inhibit the development of a different kind of skin cancer, squamous cell carcinoma, in mice. They wondered if the drug, sold by the pharmaceutical company Pfizer under the brand names Celebrex and Onsenal, would have a similar effect on the more common basal cell carcinoma.

Celecoxib is thought to work to prevent or slow cancer growth by interfering with the action of an enzyme called Cox-2, which causes tissue inflammation (pro inflammator). Celecoxib has both pain-killing (analgesic) and anti-inflammatory properties. Chronic inflammation has long been associated with the development of many types of cancer, and celecoxib has been shown in clinical trials to reduce the incidence of colon cancer in people with a genetic predisposition to the disease.

Interestingly, researchers stopped the clinical trials in 2003 (from 2001) when the study lead to high risk  of heart attack and stroke in patients taking a different NSAID. (Rofecoxib,  Vioxx by  Merck & Co. was withdrawn from the market by Merck in 2004  and Tang's trial was discontinued that year in response to ongoing concerns about long-term treatment with Cox-2 inhibitors). At that time, most participants had received about two years of drug treatment. No patient died or suffered adverse cardiovascular events due to their participation in the trial. Although drug treatment had been discontinued, the researchers continued to monitor basal cell carcinoma formation in people who had received the drug or placebo for an additional year to complete the three-year study. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumors by about 50 percent as compared to placebo in participants who entered the trial with 15 or fewer basal cell carcinomas. Celecoxib treatment also reduced the overall tumor burden in the  group of patients (where in the carcinomas are removed upon diagnosis in most people).

Now the lead researcher Dr. Tang is continuing her focus on skin cancer prevention at Stanford. She's currently investigating whether it's possible to develop a topical formulation of the drug that can be applied directly to the skin to achieve a similar protective effect without associated cardiovascular risk. Hope she will get positive results via topical formulation .....

In my opinion  its really a great achievement.We know that compounds with selective inhibitors of 5-LO (Lipoxygenase) and COX (Cyclooxegenase, that too COX-II) will be  the best NSAIDs without any ulcerogenecity, its good see that the  same compounds can be used to treat skin cancer....

Ref : http://med.stanford.edu/ism/2010/january/tang.html

Sulindac inhibits tumor growth !...

We know that, Sulindac(structure), is useful in the treatment of acute or  chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAID's except for drugs of the COX-2 inhibitor class. The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Now researchers from Sanford-Burnham Medical Research Institute (Sanford-Burnham) and their colleagues have figured out how  Sulindac, inhibits tumor growth. The study reveals that Sulindac shuts down cancer cell growth and initiates cell death by binding to nuclear receptor RXRα, a protein that receives a signal and carries it into the nucleus to turn genes on or off. 

As per the claim by the researchers, RXRα normally suppresses tumors, but many types of cancer cells produce a truncated form of this nuclear receptor that does just the opposite. This study showed that shortened RXRα enhances tumor growth by stimulating other proteins that help cancer cells survive. Luckily, the researchers also found that Sulindac can be used to combat this deviant RXRα by switching off its pro-survival function and turning on apoptosis, a process that tells cells to self-destruct.  The interesting part of their research lies in the fact that, they were able to overcome the limitation (cardiovascular side effects associated with Sulindac and other NSAIDs), the researchers tweaked Sulindac, creating a new version of the drug now called K-80003 that both decreases negative consequences and increases binding to truncated RXRα..

"Depending on the conditions, the same protein, such as RXRα, can either kill cancer cells or promote their growth," Dr. Zhang said. "The addition of K-80003 shifts that balance by blocking survival pathways and sensitizing cancer cells to triggers of apoptosis."

Ref :  http://www.cell.com/cancer-cell/retrieve/pii/S1535610810001595

FDA Approves Xifyrm (meloxicam) Injection for the Management of Moderate-to-Severe Pain in Adults

In continuation of update on Meloxicam

Azurity Pharmaceuticals, Inc.  announced the U.S. Food and Drug Administration (FDA)  approval of  Xifyrm (meloxicam injection) an IV non-steroidal anti-inflammatory drug (NSAID) that offers once daily dosing.

Xifyrm is indicated for use in adults for the management of moderate-to-severe pain, alone or in combination with non-NSAID analgesics. Xifyrm provides a non-opioid analgesic in a 30mg/mL vial for IV bolus injection over 15 seconds. Because of delayed onset of analgesia, Xifyrm alone is not recommended for use when rapid onset of analgesia is required.

“Xifyrm demonstrates our commitment to improving patient care by providing an alternate dosage form for pain management,” said Ron Scarboro, CEO at Azurity Pharmaceuticals. “Xifyrm addresses an important clinical need, especially for patients requiring a non-opioid component to multimodal analgesia strategies.”

Xifyrm will be available in the coming weeks. For full prescribing information, including boxed warning and safety profile, please visit www.Xifyrm.com

https://en.wikipedia.org/wiki/Meloxicam

FDA Approves Xifyrm (meloxicam) Injection for the Management of Moderate-to-Severe Pain in Adults

Pain reliever shows anti-viral activity against flu

In continuation of my update on naproxen

New influenza vaccines must be developed annually, because the surface proteins they target mutate rapidly, the way cars used to get a whole new look every year. The researchers, led by Anny Slama-Schwok of the Institut National de la Recherche Agronomique, Jouy en Josas, France, found a much more stable, reliable target for anti-influenza activity. The so-called ribonucleoprotein complexes are necessary for replication, and the researchers realized they could target the nucleoprotein, preventing assembly of the complexes. Because of its vital function, the nucleoprotein is highly conserved, making it a good potential target for antiviral drugs.

The nucleoprotein's three dimensional structure, solved in 2006, provided the basis for searching for new drugs that could interfere with its action. The researchers did a virtual screening within the Sigma-Aldrich online catalog of biochemicals. That screening identified Naproxen, better known as the over-the-counter pain reliever Aleve, and as expected, it bound to the nucleoprotein, and impeded RNA binding, says Slama-Schwok. In further testing, it reduced the viral load in cells infected with H1N1 and H3N2 influenza A virus, and in mice it demonstrated a therapeutic index against influenza A that was superior to that of any other anti-inflammatory drug.

Specifically, naproxen blocks the RNA binding groove of the nucleoprotein, preventing formation of the ribonucleoprotein complex, thus taking the vital nucleoproteins out of circulation. The researchers write that naproxen is a lead compound for drug development that could be improved by tweaking the molecule to boost its ability to bind to nucleoprotein.

As an already approved drug, naproxen could become a treatment against influenza relatively quickly, the researchers write. Its status as a non-steroidal anti-inflammatory drug (NSAID), which inhibits the COX-2 pathway, as well as an antiviral would boost its efficacy.

Ref : http://aac.asm.org/content/early/2013/02/26/AAC.02335-12.abstract?sid=e3391873-6ffe-4f2e-8737-685e5f2ca15f

Pain reliever shows anti-viral activity against flu

Meloxicam recognizes and treats osteoarthritis in cats

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and fever reducer effects. It is a derivative of oxicam, closely related to piroxicam, and falls in the enolic acid group of NSAIDs. It was developed by Boehringer-Ingelheim.

Meloxicam recognizes and treats osteoarthritis in cats

Naproxcinod a better NSAID.....

I knew  about Naproxen, because my first job was with Rallis India  Limited and the pharma division (sold to Shreya Group) was selling it as  a gel. It works by inhibiting both the COX-1 and COX-2 enzymes and that is the reason, why it has side effects. It has  been established already that the selective inhibitors of  COX-2 & 5 -LO will be the best drugs with least or no ulcerogenecity. We have  some drug like Celecoxib with selective inhibition of COX-2 (cyclo oxygenase enzyme), still we need to have selective inhibitors of both COX-2 & 5 -LO, so that  there will not be any cases like Rofecoxib withdrawal.

Naproxcinod, is a nitroxybutyl ester of naproxen. The ester group allow it to also act as a nitric oxide donor. Interestingly, this second mechanism of action makes naproxcinod the first of a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are expected to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects.  Now NicOx S.A announced that European Medicines Agency (EMEA) has validated the Marketing Authorization Application (MAA) for naproxcinod. NicOx is seeking approval for an indication for the relief of the signs and symptoms of primary osteoarthritis. This follows the acceptance for filing of a New Drug Application (NDA) by the US Food and Drug Administration (FDA) in November 2009.

More interestingly, in addition to naproxcinod, NicOx's pipeline includes several nitric oxide- donating NCEs, which are in development internally and with partners, including Merck & Co., Inc., for the treatment of widespread eye diseases, cardiometabolic diseases, hypertension and dermatological disease.

Details of the press release, one can read at the link....

Vardenafil (PDE5 inhibitor) as antiulcer agent?

Vardenafil, (Levitra, Bayer) is a PDE5 inhibitor used for treating impotence (erectile dysfunction). Vardenafil's indications and contra-indications are the same as with other PDE5 inhibitors; it is closely related in function to sildenafil citrate (Viagra) and tadalafil (Cialis). Structurally, the difference between the vardenafil molecule and sildenafil citrate is a nitrogen atom's position and the change of sildenafil's piperazine ring methyl group to an ethyl group. Tadalafil is structurally different from both sildenafil and vardenafil. Vardenafil's relatively short effective time is comparable to but somewhat longer than sildenafil's.

We know that most of the NSAIDs are associated with ulcerogenecity. Though there are many compounds with different mode of action have been tested (and some of them are being used) to treat the peptic ulcer, compounds with phosphodiesterase 5 inhibitor were not tested before Dr. Karakaya of Zonguldak Karaelmas University-who have reported that Vardenafil can be used to treat the NSAID-induced gastric ulcer. As per the claim by the researchers the activity is dose dependent.

Ref : http://www.wjgnet.com/1007-9327/abstract_en.asp?f=5091&v=15

A new drug to manage resistant chronic pain

BL-7050 is a new chemical entity based on the molecular structure of diclofenac (Voltaren), a well-known non-steroidal anti-inflammatory drug (NSAID) widely used in the treatment of nociceptive and inflammatory pain. However, BL-7050 operates via a novel mechanism of action, namely opening specific potassium channels in nerve cells. The opening of these channels reduces the activity of the nerve cells, thereby reducing or preventing pain signals.

Neuropathic pain is a complex, chronic state of pain that results from dysfunctional or injured nerve fibers. Neuropathic pain is associated with various conditions, including shingles, diabetes and cancer and is reported to affect 1% to 3% of the population. Patients describe the symptoms as burning, stabbing, electric shock or itching sensations, which can cause extreme discomfort for extended periods of time. A variety of medications are used to treat neuropathic pain, including antidepressants and anti-seizure medicines. However, these medications have significant side effects and are not always effective.  

If this drug ultimately proves itself though all the phase clinical trials to be successful, Anaysts see it receiving possible Orphan drug status to be prescribed to patients suffering from extreme pain caused by such diseases as terminal late stage cancers and cystic fibrosis, for example.

Ref : http://www.biolinerx.com/default.asp?pageid=14&itemid=24

A new drug to manage resistant chronic pain

Tolfenamic acid appears to reduce esophageal tumors

A new study by researchers at MD Anderson Cancer Center Orlando finds that Tolfenamic acid (TA, see structure), a non-steroidal anti-inflammatory drug (NSAID), commonly used to relieve pain, inflammation and migraines has now been found to reduce esophageal tumors.

The study, led by Pius Maliakal, PhD and Riyaz Basha, PhD, researchers at MD Anderson Orlando's Cancer Research Institute, found that Tolfenamic acid prevented tumor growth and lessened the size of esophageal tumors in a rat model. Tolfenamic acid has been found to decrease certain proteins that are critical for cancer cell growth and the progression of esophageal tumors.

MD Anderson Orlando researchers are at the forefront of Tolfenamic acid research. It was this same research team that found that Tolfenamic acid inhibits tumor growth in pancreatic cancer. MD Anderson Orlando is poised to begin a new Phase I Clinical Trial for pancreatic cancer patients using Tolfenamic acid in a few months.

Further research will be required before Tolfenamic acid can be used as a safe and effective drug for esophageal cancer prevention. At present, this drug is an approved anti-inflammatory agent in Europe, South America and Asia, but is not yet approved for use in the United States.

Tolfenamic acid appears to reduce esophageal tumors

Scientists Spot How Cox-2 Painkillers Raise Heart Risks

In continuation of my update on COX-II inhibitors....

New research has uncovered how some cox-2 painkillers increase the risk for both heart attacks and stroke. The once popular cox-2 drugs, Vioxx and Bextra, were pulled off the market in 2004 and 2005, respectively, after research showed that both raised the chances of cardiovascular trouble. Meanwhile, Celebrex, a painkiller in the same drug class that remains on the market, carries a "black box" warning alerting patients to potential heart risks.

Now, a team of scientists from the University of Pennsylvania in Philadelphia say that, although cox-2 inhibitors are very good at inhibiting the workings of the cox-2 enzyme -- and thereby easing pain -- they also throw off the cardiovascular system's delicate balance by inhibiting an enzyme that relaxes blood vessels and guards against clotting.

"It's really about a rock and a hard place," said Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston. "There's a balance in the bloodstream of clotting and vasoconstriction, as well as protection against clotting and vasodilation, which means that there's a constant balance of clotting and preventing clotting, and constricting arteries and dilating arteries."

"But with cox-2 inhibitors, they have found that you knock the protective side of that balance off," Cannon said. "And then you're left only with the constrictive part, which means the drugs up the risk for clotting and arterial constriction."

"This problem is bigger than just Vioxx, which no longer exists," he added. "It applies to every single NSAID (non-steroidal anti-inflammatory drug), because with all NSAIDs -- including Celebrex and ibuprofen, which zillions of people take -- the same issue exists. You block out the good stuff and leave the bad stuff unchecked. The one exception is Naproxen, which has an anti-platelet effect that seems to work against stroke and heart attack risk."

"Sometimes you have to take a cox-2 because you have really bad daily pain," said Cannon. "But this is a dose-dependent problem, with the more cox-2 you take the greater the cardiovascular risk. So you have to limit the dose and take the least amount you can get away with, so you can try to control crippling pain but also try not to poison your blood vessels and predispose yourself to clotting and high blood pressure."

Ref : http://stm.sciencemag.org/content/4/132/132ra54.abstract?sid=25c1e6c3-e6ee-449c-ae09-b83f14efc9f2

FDA Approves Consensi (amlodipine and celecoxib) for Treatment of Hypertension and Osteoarthritis Pain

  

In continuation of my update on amlodipine and celecoxib

Kitov Pharma Ltd. an innovative bio pharmaceutical      co.,  announced  that the U.S. Food and Drug Administration (FDA) has approved Consensi (amlodipine and celecoxib) oral tablets for marketing.                               amlodipine                                                     celecoxib      

Consensi is a patent-protected combination of celecoxib, a non-steroidal anti-inflammatory drug (NSAID), and amlodipine besylate, an antihypertensive calcium channel blocker. Consensi was approved for once daily use in three dosage forms, corresponding to the current approved dosages of amlodipine (2.5, 5, and 10 mg) for hypertension and a 200 mg dose of celecoxib for the treatment of osteoarthritis pain.

“We are very pleased with Consensi’s approval and would like to thank the members of Kitov’s team, consultants and investigators, as well as the FDA’s Division of Cardiovascular and Renal Products, for all of their support and assistance,” said Dr. J. Paul Waymack, Chairman of Kitov's Board and Chief Medical Officer. “Consensi provides a safe and effective combination treatment option for the millions of Americans who suffer from osteoarthritis pain and hypertension.

“Now that Consensi has been approved for marketing, our clinical and regulatory teams will focus on leveraging their drug development expertise to advance NT219, an exciting investigational new drug candidate currently in development for various oncology indications.”

Isaac Israel, Kitov’s CEO, added: “This approval demonstrates the Kitov team’s ability and experience in expertly guiding Consensi through clinical trials and regulatory review, from Investigational New Drug (IND) submission to FDA approval in less than four years.

“Over 50 million Americans suffer from osteoarthritis. About 1 of 3 U.S. adults or about 75 million people have high blood pressure*, known as the “silent killer” due to the absence of noticeable symptoms. As a result, patients’ adherence to the hypertension treatment regimen is low. We believe that Consensi, as a single pill combination treatment for osteoarthritis and hypertension, presents a unique value proposition of potentially increasing treatment adherence.

“We recently expanded our commercialization network for Consensi by securing a second licensing agreement in Asia with a major Chinese pharmaceutical company. The FDA approval of Consensi puts us in a stronger position towards securing commercial partnerships for the U.S. and other key territories.”

The FDA-approved Consensi New Drug Application included the positive results from the Company’s Phase III clinical trial. These data demonstrated that the study met its primary endpoint of showing that the drug lowers daytime systolic blood pressure by at least 50% of the reduction in blood pressure achieved in patients treated with amlodipine besylate only, with statistical significance of p=0.001. Kitov also submitted the positive results from its randomized double-blind, placebo-controlled renal function Phase III/IV clinical trial of Consensi. Data from this study validated the primary efficacy endpoint achieved in the completed Phase III clinical trial. This study also demonstrated that treatment with Consensi led to a statistically significant reduction of serum creatinine, a marker of renal function, from its baseline value (p=0.0005), demonstrating improved renal function in patients treated with the combination. In contrast, neither amlodipine besylate nor placebo lowered creatinine to a statistically significant level.

New anti-inflammatory drug shows promise for treating inflammatory disorders

In one of my earlier blog, I  did mention about the antiinflammatory activity of H₂S gas. Now interestingly John Wallace, a pharmacologist and director of the Farncombe Family Digestive Health Research Institute at McMaster University, compared naproxen, a commonly used NSAID, to a novel anti-inflammatory drug, ATB-346 (ATB-346 is a derivative of naproxen which releases hydrogen sulfide), which he developed in collaboration with a team of Italian chemists and is now commercializing through his company, Antibe Therapeutics Inc. The basis for this research is by the fact that hydrogen sulphide is an important mediator of gastric mucosal defence. As we all know the ulcerogenecity associated with NSAIDs, there is a need to have NSAIDs with least or no ulcerogenecity.

As per the claim by the researchers, ATB-346, [above, structure : 2-(6-methoxy-napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester] acts by inhibiting cyclooxygenase-1 and 2 and  reduces inflammation (in vivo). More interesting out come from their research is  that ATB-346 suppressed gastric prostaglandin E₂ synthesis as effectively as naproxen, but produced negligible damage in the stomach and intestine. 

ATB-346 did not cause significant damage, where as naproxen rendered significant  gastric mucosa damage (e.g. ablation of sensory afferent nerves, inhibition of endogenous nitric oxide or hydrogen sulphide synthesis, co-administration with aspirin, antagonism of K_IR6.x channels). Unlike naproxen and celecoxib, ATB-346 accelerated healing of pre-existing gastric ulcers. In a mouse airpouch model, ATB-346 suppressed cyclooxygenase-2 activity and inhibited leukocyte infiltration more effectively than naproxen. ATB-346 was as effective as naproxen in adjuvant-induced arthritis in rats, with a more rapid onset of activity, but with substantially reduced gastrointestinal toxicity (100 times safer than naproxen). Unlike naproxen, ATB-346 did not elevate blood pressure in hypertensive rats.

The researchers concluded that H2S-releasing NSAIDs appear to represent a promising alternative to existing therapies for the treatment of inflammation and pain. Future research will focus on the potential cardiovascular benefits of these drugs. .....

Ref : John L Wallace et. al., British Journal of Pharmacology, 159(6),  1236 - 1246

Salsalate may be useful for the treatment of patients with type 2 diabetes .....

We know that Salsalate (see structure; source Drugs.com)  is a  non-steroidal anti-inflammatory drug (NSAID) belonging to salicylates. It is used in the treatment of Osteo Arthritis and  Rheumatoid Arthritis. 

Now researchers from Harvard Medical School, lead by Dr. Allison Goldfine, have come up with interesting finding, i.e., Salsalate may be useful for the treatment of patients with type 2 diabetes as well. In a three-month trial of people with type 2 diabetes ,  those who took the drug showed significantly improved blood glucose levels. 

Starting off, the patients all had levels of hemoglobin A1C (a standard measurement that reflects blood sugar levels over several months) in the range of 7.0 to 9.5%. A significant number of those who took salsalate saw this number drop by 0.5%, a result that is in the range of several recently released diabetes therapeutics. Other tests related to glucose levels also showed substantial improvement.  

Overall the drug appeared to be safe and to be tolerated well by patients. The study included 108 individuals, aged from 18 to 75 years, at 17 clinical sites around the United States. Patients were randomly divided into four; three groups were each given differing amounts of salsalate in three daily doses, while the fourth received placebos. All patients continued with their current regimes for managing diabetes.

Though these preliminary findings  suggests  that,   salsalate may provide an effective, safe and inexpensive new avenue for diabetes treatment, however the researchers  want to complete the ongoing  additional studies so that they can further substantiate their claim........

Ref : March 16 in the Annals of Internal Medicine

Commonly used anti-inflammatory drug shows potential to treat Alzheimer's disease

A research project has shown that an experimental model of Alzheimer's disease can be successfully treated with a commonly used anti-inflammatory drug.

A team led by Dr David Brough from The University of Manchester found that the anti-inflammatory drug completely reversed memory loss and brain inflammation in mice.

Nearly everybody will at some point in their lives take non-steroidal anti-inflammatory drugs; mefenamic acid, a common Non-Steroidal Anti Inflammatory Drug (NSAID), is routinely used for period pain.

The findings are published today in a paper authored by Dr Brough and colleagues, in the respected journal Nature Communications. Dr Brough and Dr Catherine Lawrence supervised PhD student Mike Daniels, and postdoc Dr Jack Rivers-Auty who conducted most of the experiments.

Though this is the first time a drug has been shown to target this inflammatory pathway, highlighting its importance in the disease model, Dr Brough cautions that more research is needed to identify its impact on humans, and the long-term implications of its use.

The research, funded by the Medical Research Council and the Alzheimer's Society, paves the way for human trials which the team hope to conduct in the future.

Around 500,000 people in the UK have Alzheimer's disease which gets worse over time, affecting many aspects of their lives, including the ability to remember, think and make decisions.

In the study transgenic mice that develop symptoms of Alzheimer's disease were used. One group of 10 mice was treated with mefenamic acid, and 10 mice were treated in the same way with a placebo.

The mice were treated at a time when they had developed memory problems and the drug was given to them by a mini-pump implanted under the skin for one month.

Memory loss was completely reversed back to the levels seen in mice without the disease.

Dr Brough said: "There is experimental evidence now to strongly suggest that inflammation in the brain makes Alzheimer's disease worse.

"Our research shows for the first time that mefenamic acid, a simple Non-Steroidal Anti Inflammatory Drug can target an important inflammatory pathway called the NLRP3 inflammasome , which damages brain cells."

He added: "Until now, no drug has been available to target this pathway, so we are very excited by this result.

"However, much more work needs to be done until we can say with certainty that it will tackle the disease in humans as mouse models don't always faithfully replicate the human disease."Because this drug is already available and the toxicity and pharmacokinetics of the drug is known, the time for it to reach patients should, in theory, be shorter than if we were developing completely new drugs.

"We are now preparing applications to perform early phase II trials to determine a proof-of-concept that the molecules have an effect on neuroinflammation in humans."

Dr Doug Brown, Director of Research and Development at Alzheimer's Society, said: "Testing drugs already in use for other conditions is a priority for Alzheimer's Society - it could allow us to shortcut the fifteen years or so needed to develop a new dementia drug from scratch.

"These promising lab results identify a class of existing drugs that have potential to treat Alzheimer's disease by blocking a particular part of the immune response. However, these drugs are not without side effects and should not be taken for Alzheimer's disease at this stage - studies in people are needed first."

Commonly used anti-inflammatory drug shows potential to treat Alzheimer's disease

Steroid May Be Safe, Effective Gout Treatment, Study Finds

A steroid pill may be as good as a nonsteroidal anti-inflammatory drug (NSAID) for treating painful gout, new research suggests.

Researchers who compared the steroid prednisolone with the arthritis medication indomethacin found both drugs offered a similar degree of pain reduction. And while indomethacin (Indocin) appeared to cause more minor side effects, neither treatment prompted serious complications, the researchers said.

        (Prednisole) (Indomethacin)

Smaller investigations have pointed in the same direction, said study lead author Dr. Timothy Rainer, a professor of emergency medicine at Cardiff University in Wales. But because the new findings are the product of a "larger and better-designed" effort, Rainer said steroid pills may gain standing among gout experts who usually stick with NSAIDs as their first-line treatment.

The bottom line is that there are choices, said Dr. Philip Mease, a rheumatologist with the Swedish Medical Center in Seattle.

"That is the key message - that there are options," said Mease, who wasn't involved in the study. "Sometimes ER docs don't think about giving a tapering dose of prednisone, but it can be very effective at helping with gout, which can be damn painful."

Steroid May Be Safe, Effective Gout Treatment, Study Finds