Neuronal Nicotinic Receptors - November 2008
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Neuronal nicotinic receptor ligands are fast proceeding through clinical development as exciting candidates for multiple CNS disorders including Alzheimer's disease; Schizophrenia; ADHD; Depression; Pain and Addiction.
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Table of Contents
What's in the November 2008 edition of UpdatesPlus-Nicotinic Receptors?
- Your guide to Neuroscience, 2008: We have collected most of the key nicotinic presentations for Neuroscience and analysed them
- Memory Pharmaceuticals - An update: November 2008 was a big month for Memory Pharmaceuticals. Starting off with the company's Q3 presentation Memory made a number of key announcements including further information on its phase 2 CIAS study evaluating R3487/MEM 3454. How is this trial advancing? We make our forecasts and discuss the progress of this likely first-in-class α7 agonist. We also provide an update on the development of this candidate for Alzheimers disease. Perhaps the biggest news around Memory however is the announcement of its acquisition by Roche.
- Beta amyloid and alpha 7 receptors - what is their relationship and how should this be targeted: A number of posters were presented at Neuroscience discussing the interaction between Aß and α7 receptors. Data were presented demonstrating that the α7 agonist S 24795 prevents Aß42 from binding and desensitizing α7 receptors. Long-term internalization of Aß42 was also prevented. This suggests that blocking Aß:alpha 7 receptor interaction may be beneficial in the treatment of Alzheimer's disease. On the other hand, another paper suggested that interaction of Aß with α7 receptors is important in the physiology of memory and that blocking this interaction could be detrimental. Moreover amyloid mimics could be of benefit to some cognitive disorders.
- Development of SEN12333/WAY-317538: SEN12333 (WAY-317538) is a full α7 agonist being developed by Siena Biotech in collaboration with Wyeth. Preclinical data have previously been presented supporting the development of SEN12333 as a treatment of Alzheimer’s disease. Data have now been presented supporting its potential use as a treatment of schizophrenia.
- Advancement of PAMs: Two types of positive allosteric modulators of the α7 receptor exist: type I and type II. UpdatesPlus presents one candidate from each class. Abbott has announced a new type II PAM, A-867744; Xytis is about to advance the type I positive allosteric modulator, XY4083 into the clinic.
- Nictonic receptor agonists - exciting new targets for the treatment of arthritis: α7 receptor agonsits have recently emerged as candidate treatments of inflammatory pain; this month we highlight data supporting their development as anti-inflammatory agents. The direct targeting of two of the cardinal aspects of arthritis, pain and inflammation suggests that nicotinic receptor agonists should be fully evaluated as candidates of both rheumatoid and osteoarthritis
- ABT-894 - Will it succeed: Abbott stopped the development ABT-594 due to gastrointestinal adverse events. ABT-894 has an improved therapeutic index but nausea and vomiting may remain an issue. Read all about ABT-894 in this issue.
- The potential of ABT-089 Abbott is involved in a second α4ß2 agonist, ABT-089. This molecule is being developed in partnership with Targacept for the treatment of ADHD. ABT-089 appears to present an improved profile to other ADHD therapeutics - here we discuss preclinical data highlighting the likely lack of abuse potential and sleep disturbance
- The advance of alpha 6 receptor ligands: The November edition of UpdatesPlus introduces TC-5653, Targacept's promising α4* and α6* dual agonist. This molecule is able to rapidly reduce striatal dopamine release. Read about how this molecule could lead to a new and improved smoking cessation aid. We also present new data suggesting that receptor sensitization could offer a new approach to Parkinson's disease.
- Full and up to date pipeline
UpdatesPlus continuously tracks development activity behind all known nicotinic agonists, antagonists and modulators
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2008 issues:
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