|
||
| |||||||
|
Modulators of VR1: A novel approach to analgesia Chronic pain affects 40-70 million people per year in the US alone and represents a serious and multi-factorial clinical problem. Furthermore, establishing prolonged analgesia free of serious side effects is a particularly challenging area of medicine. The total economic cost of pain is US$100 billion and global sales of analgesics and anti-inflammatories have been estimated as US$18.7 billion worldwide. Analgesia is currently treated by NSAIDs or by opiates. The former is related to well-publicized and serious GI problems while the latter causes unwanted side central side effects. New analgesics are therefore urgently required (see our recent feature "Future Pain Drugs" for a full analysis of this field). Capsaicin and other similar molecules such as resiniferatoxin have been targeted as therapeutic approaches to analgesia, however this field took a major step forward in 1997 following the identification of the vanilloid receptor VR1 and more recently other member of this receptor family. Consequent advances in vanilloid pharmacology are now starting to produce therapeutic candidates and indeed the number of vanilloid ligands in pharmaceutical development has doubled over the past year. While the identification of receptor ligands offers one therapeutic approach, the identification of modulators of its channel activity represents an alternative strategy. Capsaicin responses in sensory neurons exhibit robust potentiation by cAMP-dependent protein kinase (PKA). Most recently Baylor researchers demonstrate that PKA reduces VR1 desensitization and directly phosphorylates VR1. In vitro phosphorylation, phosphopeptide mapping, and protein sequencing of VR1 cytoplasmic domains delineate several candidate PKA phosphorylation sites. Electrophysiological analysis of phosphorylation site mutants clearly pinpoints Ser116 as the residue responsible for PKA-dependent modulation of VR1. Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury. Furthermore the identification of molecules able to prevent this molecular interactions should offer significant therapeutic potential. Entry date October, 2002 Adapted from Bhave et al, Neuron 2002 Aug 15;35(4):721-31
Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk LeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
|
| ||||||||
