Lamotrigine

Scientists have discovered genetic clues to the cause of restless leg syndrome, a condition common among older adults. The discovery could help identify those individuals at greatest risk of the condition and point to potential ways to treat it. Scientists have discovered genetic clues to the cause of restless leg syndrome, a condition common among older adults. The discovery could help identify those individuals at greatest risk of the condition and point to potential ways to treat it. Restless leg syndrome can cause an unpleasant crawling sensation in the legs and an overwhelming urge to move them. Some people experience the symptoms only occasionally, while others get symptoms every day. Symptoms are usually worse in the evening or at night-time and can severely impair sleep. Despite the condition being relatively common -- up to one in 10 older adults experience symptoms, while 2-3% are severely affected and seek medical help -- little is known about its causes. People with restless leg syndrome often have other conditions, such as depression or anxiety, cardiovascular disorders, hypertension, and diabetes, but the reason why is not known. Previous studies had identified 22 genetic risk loci -- that is, regions of our genome that contain changes associated with increased risk of developing the condition. But there are still no known 'biomarkers' -- such as genetic signatures -- that could be used to objectively diagnose the condition. To explore the condition further, an international team led by researchers at the Helmholtz Munich Institute of Neurogenomics, Institute of Human Genetics of the Technical University of Munich (TUM) and the University of Cambridge pooled and analysed data from three genome-wide association studies. These studies compared the DNA of patients and healthy controls to look for differences more commonly found in those with restless leg syndrome. By combining the data, the team was able to create a powerful dataset with more than 100,000 patients and over 1.5 million unaffected controls. The results of the study are published today in Nature Genetics. Co-author Dr Steven Bell from the University of Cambridge said: "This study is the largest of its kind into this common -- but poorly understood -- condition. By understanding the genetic basis of restless leg syndrome, we hope to find better ways to manage and treat it, potentially improving the lives of many millions of people affected worldwide." The team identified over 140 new genetic risk loci, increasing the number known eight-fold to 164, including three on the X chromosome. The researchers found no strong genetic differences between men and women, despite the condition being twice as common in women as it is men -- this suggests that a complex interaction of genetics and the environment (including hormones) may explain the gender differences we observe in real life. Two of the genetic differences identified by the team involve genes known as glutamate receptors 1 and 4 respectively, which are important for nerve and brain function. These could potentially be targeted by existing drugs, such as anticonvulsants like perampanel and lamotrigine, or used to develop new drugs. Early trials have already shown positive responses to these drugs in patients with restless leg syndrome. The researchers say it would be possible to use basic information like age, sex, and genetic markers to accurately rank who is more likely to have severe restless leg syndrome in nine cases out of ten. To understand how restless leg syndrome might affect overall health, the researchers used a technique called Mendelian randomisation. This uses genetic information to examine cause-and-effect relationships. It revealed that the syndrome increases the risk of developing diabetes. Although low levels of iron in the blood are thought to trigger restless leg syndrome -- because they can lead to a fall in the neurotransmitter dopamine -- the researchers did not find strong genetic links to iron metabolism. However, they say they cannot completely rule it out as a risk factor. Professor Juliane Winkelmann from TUM, one of senior authors of the study, said: "For the first time, we have achieved the ability to predict restless leg syndrome risk. It has been a long journey, but now we are empowered to not only treat but even prevent the onset of this condition in our patients."

LAFAYETTE, Calif., May 31, 2024 /PRNewswire/ -- The Alexander Shulgin Research Institute (ASRI) has unveiled a groundbreaking discovery in the journal Molecular Pharmacology: the first bifunctional compound that acts as both a 5-HT2A receptor antagonist and a voltage-gated sodium channel blocker. This novel molecule, known as XOB, could revolutionize the treatment landscape for bipolar disorder. Key Findings: Continue Reading ASRI's discovery of XOB marks a significant milestone in psychiatric pharmacology. Post this 1. XOB's Dual Mechanism of Action: ASRI Co-Founder and President, Dr. Nicholas Cozzi, spearheaded the design and synthesis of XOB. His team collaborated with experts from leading institutions, including the University of Michigan-Ann Arbor, Stanford University, Medical College of Wisconsin, Usona Institute, and Promega Corporation. Lead author Dr. Nicholas Denomme, of the University of Michigan-Ann Arbor and Stanford University, guided and performed electrophysiology studies which revealed that XOB had a blocking effect on voltage-gated sodium channels in cultured cells and neurons. ASRI and Usona Institute scientists performed essential physical and chemical analyses of XOB, while researchers at the Medical College of Wisconsin and Promega Corporation assessed serotonin receptor binding and functional effects. 2. Potential Impact on Bipolar Disorder Treatment: Bipolar disorder management often involves a combination of drugs, such as a serotonin receptor antagonist (e.g., quetiapine) and a sodium channel blocker (e.g., lamotrigine). XOB's unique property lies in its ability to perform both functions simultaneously, at similar drug concentrations. Dr. Cozzi emphasized that XOB represents a proof-of-concept, opening doors to safer and more effective treatments for this challenging disease. 3. Polypharmacology: A New Paradigm: XOB exemplifies polypharmacology, wherein a single drug targets multiple disease-related pathways. This approach recognizes that many disorders have complex genetic origins, necessitating multifaceted therapeutic strategies. ASRI's discovery of XOB marks a significant milestone in psychiatric pharmacology. The potential to address bipolar disorder with a single, multifunctional compound could transform patient care and improve outcomes. Further research and clinical trials will determine XOB's efficacy and safety profile. Disclaimer: This press release is for informational purposes only and does not constitute medical advice. Consult a healthcare professional for personalized recommendations. About ASRI: Established on Bicycle Day in 2021 by Dr. Nicholas Cozzi, Dr. Paul Daley, and the late Ann Shulgin, ASRI continues the legacy of the esteemed chemist Alexander Shulgin, renowned for his pioneering work in discovering psychedelic compounds. At the forefront of the burgeoning interest in the potential therapeutic benefits of psychedelics, ASRI remains steadfast in its commitment to applied therapeutics, targeting neurological, neurodevelopmental, neuropsychiatric, pain syndrome, inflammation, and overall wellness enhancement domains. Drawing upon a wealth of knowledge in chemistry, pharmacology, and neuroscience, ASRI is committed to catalyzing positive change in global healthcare. Noteworthy is the Shulgin Vault, housing an extensive repository of over 500 compounds synthesized by Alexander "Sasha" Shulgin and ASRI scientists, offering a rich spectrum of novel variations spanning phenylalkylamines, tryptamines, lysergamides, isoquinolines, cathinones, and more. For more information on ASRI, please visit: . Forward-looking statement: This release contains forward-looking statements regarding ASRI's anticipated future events and outcomes, such as data projections and advancements in drug discovery methods. These statements are based on current expectations and assessments but are subject to various risks and uncertainties. Factors such as the ongoing impact of COVID-19, fluctuations in economic conditions, market dynamics, regulatory constraints, and other variables may cause actual results to differ from those anticipated. While ASRI's management has made reasonable assumptions, the actual outcomes may deviate significantly. It's important to note that ASRI has refrained from making medical assertions about its products, and regulatory bodies like the FDA have not yet evaluated their effectiveness. Rigorous clinical trials are necessary for validation, a process which ASRI has not yet undertaken. Without obtaining the required approvals or conducting essential research, ASRI's performance and operations may be negatively impacted. Therefore, stakeholders should be mindful of these uncertainties when considering the forward-looking statements contained in this release.‍ Media Contact: Kathy Lanser, [email protected] SOURCE Alexander Shulgin Research Institute