Caffeine's effect on the brain's adenosine receptors visualized for the first time

In continuation on my update on coffee

Molecular imaging with positron emission tomography (PET) has enabled scientists for the first time to visualize binding sites of caffeine in the living human brain to explore possible positive and negative effects of caffeine consumption. According to research published in the November issue of The Journal of Nuclear Medicine, PET imaging with F-18-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (F-18-CPFPX) shows that repeated intake of caffeinated beverages throughout a day results in up to 50 percent occupancy of the brain's A₁adenosine receptors.

"There is substantial evidence that caffeine is protective against neurodegenerative diseases like Parkinson's or Alzheimer's disease," noted Elmenhorst. "Several investigations show that moderate coffee consumption of 3 to 5 cups per day at mid-life is linked to a reduced risk of dementia in late life. The present study provides evidence that typical caffeine doses result in a high A₁ adenosine receptor occupancy and supports the view that the A₁ adenosine receptor deserves broader attention in the context of neurodegenerative disorders." 

Caffeine's effect on the brain's adenosine receptors visualized for the first time

New target discovered for food allergy treatment

New target discovered for food allergy treatment: Researchers have discovered a novel target for the treatment of food allergies. Levels of the enzyme Pim 1 kinase rise in the small intestines of peanut-allergic mice. Inhibiting activity of Pim 1 markedly reduced the allergic response to peanuts.

Common food preservative, Nisin may slow, even stop tumor growth

We know that, Nisin is a polycyclic antibacterial peptide with 34 amino acid residues used as a food preservative. It contains the uncommon amino acids lanthionine (Lan), methyllanthionine (MeLan), didehydroalanine (Dha) and didehydroaminobutyric acid (Dhb). These unusual amino acids are introduced by posttranslational modification of the precursor peptide. In these reactions a ribosomally synthesized 57-mer is converted to the final peptide. The unsaturated amino acids originate from serine and threonine, and the enzyme-catalysed addition of cysteine residues to the didehydro amino acids result in the multiple (5) thioether bridges. Subtilin and Epidermin are related to Nisin. All are members of a class of molecules known as lantibiotics.

Nisin is produced by fermentation using the bacterium Lactococcus lactis. Commercially, it is obtained from the culturing ofLactoccus lactis on natural substrates, such as milk or dextrose, and is not chemically synthesized.

The study is the first to show CHAC1's new role in promoting cancer cell death under nisin treatment. The findings also suggest that nisin may work by creating pores in the cancer cell membranes that allow an influx of calcium. It's unclear what role calcium plays in nisin-triggered cell death, but it's well known that calcium is a key regulator in cell death and survival.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/cam4.35/abstract;jsessionid=288DD01F2898095E16F5EEAFEF5274FD.d02t03

Common food preservative may slow, even stop tumor growth

Nabilone Drug offers new pain management therapy for diabetics.....

We know that, Nabilone is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It is a synthetic cannabinoid, which mimics the main chemical compound of cannabis(THC). Chemically, nabilone is similar to the active ingredient found in naturally occurring Cannabis sativa L. 

In Canada, the United States, the United Kingdom and Mexico, nabilone is marketed as Cesamet. It was approved in 1985 by the U.S. Food and Drug Administration (FDA) for treatment of chemotherapy-induced nausea and vomiting that has not responded to conventional antiemetics. Though it was approved by the FDA in 1985, the drug only began marketing in the United States in 2006. It is also approved for use in treatment of anorexia and weight loss in patients with AIDS.

Although it doesn't have the official indication (except in Mexico), nabilone is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrated various benefits for conditions such as fibromyalgia  and multiple sclerosis. Nabilone is a racemic mixture consisting of the (S,S) and the (R,R) isomers ("trans") ......

Ref : http://www.ucalgary.ca/news/utoday/october31-2012/pain

. Drug offers new pain management therapy for diabetics

EU Approves Dacogen, Velcade Indications | News | Drug Discovery and Development Magazine

In continuation of my update on Dacogen

EU Approves Dacogen, Velcade Indications | News | Drug Discovery and Development Magazine

Dulaglutide Fares Well in New Trials

Eli Lilly and Co.'s potential once-weekly treatment for type 2 diabetes fared better than three other drugs in lowering blood sugar levels, according to initial results from some late-stage research.

The Indianapolis drugmaker said that two doses of its injectable drug dulaglutide (see structure) delivered statistically superior reductions in blood sugar levels when compared to twice-daily injections of exenatide and the oral treatments metformin and sitagliptin. Lilly will present more details from the studies at scientific meetings next year and in 2014.

Lilly said it will submit the drug to regulators for approval next year. It said timing in the United States will depend on the completion of Food and Drug Administration requirements for an assessment of the drug's cardiovascular risk.

Dulaglutide Fares Well in New Trials 

Bayer Releases Riociguat Data

We  know that,  Riociguat (BAY 63-2521, below structure) is a novel drug that is currently in clinical development by Bayer. It is a stimulator of soluble guanylate cyclase (sGC). At the moment Phase III clinical trials investigate the use of riociguat as a new approach to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of a novel class of sGC stimulators. 

Bayer Releases Riociguat Data  

FDA Clears Eisai’s Epilepsy Drug Fycompa

We know that, Fycompa (see structure, perampanel) is a selective, non-competitive AMPA receptor antagonist discovered by the research teams at Eisai laboratories. The development of an AMPA antagonist compound with a favourable pharmacokinetic and safety profile arose after the AMPA receptor was identified as a promising target for drug development. The AMPA receptor is widely present in almost all excitatory neurons. It is believed to play a role in a large number of central nervous system diseases with similar neuropathology.

GEN | News Highlights:FDA Clears Eisai’s Epilepsy Drug Fycompa.

Inhibitory Effect of Carob (Ceratonia siliqua) Leaves Methanolic Extract on Listeria monocytogenes - Journal of Agricultural and Food Chemistry (ACS Publications)

We know that, Ceratonia siliqua, commonly known as the Carob tree and St John's-bread,  is a species of floweringevergreen shrub or tree in the pea family, Fabaceae. It is widely cultivated for its edible legumes, and as anornamental tree in gardens. The seed pod may be crushed and used as ersatz chocolate.

It is native to the Mediterranean region including Southern Europe, Northern Africa, the largerMediterranean islands; to the Levant and Middle-East of Western Asia into Iran; and to the Canary Islandsand Macaronesia

Inhibitory Effect of Carob (Ceratonia siliqua) Leaves Methanolic Extract on Listeria monocytogenes - Journal of Agricultural and Food Chemistry (ACS Publications)

Positive Results from Phase 2 Trial of Oral Calcitonin | News | Drug Discovery and Development Magazine

Tarsa Therapeutics Inc. announced that a Phase 2 trial of its oral recombinant salmon calcitonin in the prevention of postmenopausal osteoporosis was successfully concluded and yielded statistically significant, clinically relevant improvements in bone mineral density (BMD) at the lumbar spine.  These data were presented at the American Society for Bone and Mineral Research (ASBMR) 2012 Annual Meeting by Phase 2 investigator Neil Binkley, MD, who is an associate professor of endocrinology and Geriatrics at the University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin.....

Positive Results from Phase 2 Trial of Oral Calcitonin | News | Drug Discovery and Development Magazine

T-DM1 Extends Overall Survival | News | Drug Discovery and Development Magazine

We know that,Trastuzumab emtansine (INN, also called trastuzumab-DM1 or trastuzumab-MCC-DM1, abbreviated T-DM1) is an antibody-drug conjugate consisting of the antibody trastuzumab (the active ingredient in Herceptin) linked to a cytotoxic agent that is a derivative of maytansine (DM1).

It is in clinical trials for breast cancer, especially of the HER2 positive type. Early results in Nov 2011 from an open-label phase II trial on 137 patients with HER2-positive advanced breast cancer were very encouraging.

EMILIA, a phase III trial of 991 people with HER2-positive unresectable locally advanced or metastatic breast cancer, comparing T-DM1 versus capecitabine plus lapatanib in patients previously treated with trastuzumab and a taxane chemotherapy, showed improved progression free survival in patients treated with T-DM1 (median 9.6 vs. 6.4 months) with an improved safety profile. The study sponsor reported in August 2012 that T-DM1 significantly improved survival in the EMILIA study and that the details will be reported at an upcoming medical meeting

T-DM1 Extends Overall Survival | News | Drug Discovery and Development Magazine

FDA Approves Oxtellar...

Oxtellar XR  is Oxcarbazepine Extended-Release Tablets...

We know that, Oxcarbazepine  is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy. It is also used to treat anxiety and mood disorders, and benign motor tics. Oxcarbazepine is marketed as Trileptal by Novartis and available in some countries as a generic drug.

FDA Approves Oxtellar | News | Drug Discovery and Development Magazine

Astex Begins Phase 2 Cancer Trial | News | Drug Discovery and Development Magazine

Astex Begins Phase 2 Cancer Trial of  SGI-110 | News | Drug Discovery and Development Magazine

Empagliflozin Lowers Blood Pressure | News | Drug Discovery and Development Magazine

We know that, Empagliflozin (see structure) is a SGLT2 inhibitor which is being investigated in clinical trials for the oral treatment of type 2 diabetes by Boehringer Ingelheim and Eli Lilly and Company. It is an inhibitor of the sodium glucose co-transporter-2 (SGLT-2), which is found almost exclusively in the proximal tubules of nephronic components in the kidneys. SGLT-2 accounts for about 90 percent of glucose reabsorption into the blood. Blocking SGLT-2 causes blood glucose to be eliminated through the urine via the urethra...

Empagliflozin Lowers Blood Pressure | News | Drug Discovery and Development Magazine   ....

Aveo Files Tivozanib NDA | News | Drug Discovery and Development Magazine

We know that, Tivozanib (see structure below, AV-951) is an oral VEGF receptor tyrosine kinase inhibitor. It is undergoing clinical trial investigation for the treatment of renal cell carcinomas.An oral quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor. It was developed by AVEO Pharmaceuticals.It is designed to inhibit all three VEGF receptors. Phase III results on advanced renal cell carcinoma suggest a 30% or 3 months improvement in median PFS compared tosorafenib. 

Aveo Files Tivozanib NDA | News | Drug Discovery and Development Magazine