Combating mood disorders: New approach simplifies the search for more specific drugs

Many psychiatric conditions are caused by aberrant metabolism of the neurotransmitter serotonin. Researchers in the Department of Pharmacy at LMU have now developed a new screening method, which will facilitate the search for new drugs that modulate the biological activity of serotonin.

Psychiatric ailments such as depression, obsessive-compulsive disorder or anxiety states are often associated with disturbances in the metabolism of the neurotransmitter serotonin. Neurotransmitters are compounds that are released from the synapses at nerve cell endings and activate the firing of neighboring neurons. Thus, as their name suggests, they mediate the transmission of nerve impulses. The serotonin transporter (SERT) is responsible for reuptake of the transmitter into neurons, terminating its action. SERT is a major target for drugs that are used to treat many mood disorders, and the search for new SERT inhibitors is of continuing therapeutic relevance. A research team led by Professor Klaus Wanner of the Department of Pharmacy in the Center for Pharmaceutical Research at Ludwig-Maximilians Univeristät München (LMU) has now developed a novel binding assay, based on the use of mass spectrometry (MS), which promises to simplify the search for potential SERT inhibitors very significantly. The major advantage of the technique is that, unlike conventional binding assays, it avoids the need to use radiolabeled substances. A paper that describes the new assay will appear in the journal ChemMedChem on 4. October. The article has been rated as a "very important paper" and is featured on the cover of the upcoming issue of the journal.

To be effective, most drugs must bind selectively to defined molecular targets in the body. The target may be an enzyme found in certain cells or a protein on the plasma membrane of a specific cell type. Drug candidates must therefore be assessed for their affinity for the target by means of binding assays. These assays often involve the use of a chemical that is already known to recognize and bind selectively to the target as. The ability of a test substance to find and interact with the target is then measured in terms of how well it competes with this "marker" ligand. The greater its ability to displace the marker from the binding site, the higher is its own affinity for the target, and the more likely it is to be clinically effective. In the MS-based binding assay developed by Wanner's group, quantification of the marker is carried out using mass spectrometry. In contrast to conventional techniques, which employ radiolabeled ligands, MS binding assays do not require the use of markers containing radioactive isotopes. This means that the marker can be assayed in its unaltered, native state. "This label-free technique provides all the advantages offered by classical binding studies, while avoiding the need to work with radioactive compounds," explains Wanner. His team has now validated the MS-based binding assay for use in the search for new inhibitors of SERT function. "Because SERT regulates the concentration of serotonin in the synaptic cleft, the protein serves as the major target for the treatment of depression, obsessive-compulsive disorders and anxiety states," says Wanner. Using the well-known antidepressant (S)-fluoxetine as a native marker, his group has now shown that the results of the MS-based assay are in very good agreement with those obtained using radiolabeled ligands. Indeed, the team now routinely uses the MS method to screen for novel, pharmacologically active SERT inhibitors. In addition, Wanner has plans to adapt the approach for use with other target molecules of clinical interest. (göd)

More information: (S)- and (R)-Fluoxetine as Native Markers in Mass Spectrometry (MS) Binding Assays Addressing the Serotonin Transporter.
M. Hess, G. Höfner, K. Wanner. ChemMedChem 2011, vol 6, no. 10, 4. October; First published online 26. July 2011 doi:10.1002/cmdc.201100251

Provided by Ludwig-Maximilians-Universität M?nchen

BASF to build world-scale production site for customer specific antioxidant blends

07-22-2011: BASF will significantly expand its presence in the Middle East region by building a state-of-the-art plant for customer specific antioxidant blends (CSB) in Bahrain. CSBs are key additives for the production of polymers for the plastics industry, especially for the Middle East region.

Construction of the new facility will start in September 2011. It will become one of the world’s largest CSB plants with an annual capacity of about 16,000 metric tons. The new plant will be operational already by end of 2012.

This is a major investment of BASF in the plastic additives business following its acquisition of Ciba in 2009 and manifests BASF’s strong commitment to this industry. Hans W. Reiners, President of BASF’s Performance Chemicals division, explained this strategic move: “We are very happy to establish a state-of-the-art CSB production site close to our customers in this fast growing region. This is backed by our powerful production network of antioxidants in Asia, Europe and the Americas making us worldwide one of the leading partners to the plastic processing industry with a product portfolio unmatched in terms of broadness and quality. BASF is very much committed to further strengthen its plastic additives business ranging from antioxidants
and lightstabilizers to pigments.”

This new plant will come in addition to the existing manufacturing agreement for CSBs with Astra Polymer in the Kingdom of Saudi Arabia, making BASF the largest CSB supplier in this region. This facility will be well positioned to serve the fast growing polymer market in the Middle East with special focus on key customers in the countries of the Gulf Cooperation Council (GCC), one of the fastest growing regions for the production of polyolefin resins worldwide.

“The expected growth of the plastic polymer production in Middle East will get an additional push by increasing efforts to grow the plastics downstream market locally. As BASF, we are committed to accompany such growth with technical solutions and flexible supply patterns which are only possible as a local supplier,” said John Frijns, Senior Vice President Plastics Additives Europe/EAWA. “This will help us to deliver high quality products tailor-made to the demand of the industry. Furthermore, the proximity to our main customers will ensure a flexible and reliable supply.”

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Evonik has reduced its specific energy-related greenhouse gas emissions by sixteen percent compared to 2004

Evonik Industries has significantly improved its CO2 efficiency. The Group has been able to reduce its specific energy-related greenhouse gas emissions in chemical production by sixteen percent; compared to the previous year, the improvement in 2010 was a full three percent. This is highlighted in the company’s 2010 Corporate Responsibility Report, which was recently presented in Brussels. This success means that Evonik has moved another step closer to its self-imposed goal of reducing the specific energy-related greenhouse gases of its chemical activities to twenty percent below the level of 2004 by 2014.

60 percent of CO2 emissions in 2010 were energy-related and 40 percent related to chemical processes. Absolute emissions of greenhouse gases increased to 9.14 million metric tons CO2 equivalents in 2010, a rise of 11 percent over the previous year (2009: 8.23). At the same time, specific emissions, i.e. emissions relative to output, declined by 3 percent. Accordingly, Evonik has successfully detached its production growth from rising emissions. “Our significantly increased energy efficiency is making an important contribution to climate protection" says Klaus Engel, the Chairman of the Evonik Executive Board.

With the global economy regaining momentum, the Group returned to operating its chemical production facilities at full capacity in 2010, in many cases with optimized efficiency. A number of efficiency enhancement measures contributed to the reduction of specific greenhouse gas emissions.  These included the start-up of a new cogeneration power plant in Antwerp (Belgium) and a more efficient installation for thermal incineration of exhaust gases from the production of the feed additive methionine. In addition, Evonik initiated selective energy-saving programs at its site in Rheinfelden (Germany). During the 2010 financial year, Evonik invested a total of 36 million Euro in environmental protection for its chemical business activities.

“We want to be successful as a supplier of competitive products and technologies that also make a contribution to sustainability. At the same time, we want to be a responsible, reliable and fair partner for our customers, employees and society and meet the demands made by our shareholders,” noted CEO Klaus Engel.

Evonik invested some €338 million in research and development in 2010. The Group pursued about 500 different projects, of which approximately 100 focused on resource efficiency.

The Corporate Responsibility (CR) efforts of Evonik provide answers for challenges of the future, such as resource efficiency. Says Christine Anders, Head of CR at Evonik: “Corporate Responsibility is an integral part of our business and we plan to keep fine-tuning our CR strategy in 2011.” With its three dimensions of Business, Employees, and Processes, the CR strategy is a fixed component of the corporate strategy, providing support and new impulses.  In 2010, the Group identified important sustainability topics as part of so-called materiality analyses and intensified its dialog with stakeholders.

The Evonik Corporate Responsibility Report 2010 for the first time met the requirements for the highest application level A+ of the Global Reporting Initiative (GRI). GRI is the internationally recognized standard for comprehensive sustainability reporting and confirmed the A+ reporting level for Evonik. Large parts of the report underwent a business audit by an auditing firm.