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Last Updated: Nov 17th, 2006 - 22:35:04

Anaethesia Channel
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Latest Research : Anaethesia

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Latest Data on Novel Short-acting Sedatives
Jun 2, 2005, 10:31, Reviewed by: Dr.

The data supports the desired profile of a rapid onset and rapid offset of action and organ-independent metabolism. These compounds are being developed for use as sedatives for patients undergoing short diagnostic and surgical procedures.

 
CeNeS Pharmaceuticals plc (AIM: CEN) (“CeNeS” or “the Company”) today announced that recent presentations at two anaesthesia congresses included new data on two of its product programmes: morphine-6-glucuronide (M6G) for post–operative pain and CeNeS’ short-acting sedative programme.

In a talk at the European Society for Intravenous Anaesthesia (EuroSIVA, Vienna, Austria 27th-28th May 2005 - www.eurosiva.org ) entitled ‘New Drugs for Hypnosis and Sedation’ CeNeS’ Director of Drug Discovery, Dr Gavin Kilpatrick, gave the first public presentation of data on CeNeS’ novel short-acting sedatives.

The data supports the desired profile of a rapid onset and rapid offset of action and organ-independent metabolism. These compounds are being developed for use as sedatives for patients undergoing short diagnostic and surgical procedures. CeNeS’ lead short-acting sedative compound, CNS 7056X, is in pre-clinical development.

Immediately after the EuroSIVA meeting, the European Society for Anaesthesiology meeting (ESA, Vienna, Austria 28th-31st May 2005 - www.euroanesthesia.org ) included a symposium on morphine metabolites at which the distinguished academics, Professor Albert Dahan (Leiden, The Netherlands), Dr Magdi Hanna (London, UK) and Professor Lona Christrup (Copenhagen, Denmark) presented data on M6G.

The M6G presentations included new data from Professor Christrup’s unit at the Danish University of Pharmaceutical Services on the oral bioavailability of M6G and its potential use in the treatment of chronic pain. The conclusions presented by Professor Christrup were:

1. The constant and prolonged absorption of M6G after peroral administration might represent a physiological sustained release system, useful for the treatment of chronic pain.

2. Due to its hydrophilic properties and consequently the slow rate of entering into the CNS, M6G might have a low abuse potential compared to more lipophilic opioids.

3. The prolonged duration of analgesia, which is probably due to accumulation in brain extracellular fluid, makes M6G suited for treatment of chronic pain conditions.

4. M6G appears to give rise to lesser nausea/vomiting and respiratory depression than morphine.

5. Thus M6G might prove to be a therapeutic milestone in the treatment of chronic pain.

The symposium also discussed previously released data on the use of M6G as an analgesic for the treatment of post-operative pain and its reduced tendency to cause respiratory depression compared to morphine. Overall, the feedback from the attending anaesthetists was very positive regarding the potential clinical profile of M6G.

CeNeS is developing M6G as a new treatment for post-operative pain and continues to review M6G’s additional potential for the treatment of the chronic pain market. The compound is in Phase III clinical trials in post–operative pain.

Neil Clark, Chief Executive commented: “These are two of the most prestigious annual events for anaesthetists in Europe. We are delighted to see that our programmes have achieved such a high profile and that M6G continues to gain support as a potentially significant new pain product.”


About M6G

M6G (morphine-6-glucuronide) is a potent active metabolite of morphine. Morphine is one of the most effective opioid analgesics and is widely used for the management of moderate to severe pain, including the pain experienced by patients following a wide range of surgical operations. Over 130 million surgical procedures are carried out in the seven major pharmaceutical markets annually.

Morphine is acknowledged to be the ‘gold standard’ treatment against which other parenteral analgesics are tested. Nonetheless, even after administration of morphine, various studies report that between 40-100% of patients continue to experience moderate to severe pain following surgery, indicating the clear need for new and effective treatments for postoperative pain. Morphine is also associated with a number of side effects including nausea, retching, vomiting and sedation. These side effects cause discomfort to the patient and add costs to their care by incurring the use of additional drugs to treat the side effects, as well as the costs of associated clinical and nursing care. Morphine is also associated with an increased risk of respiratory depression, a potentially fatal condition, at the higher doses required for management of severe pain.

Clinical studies have shown that M6G has an equivalent analgesic effect to morphine but also has an improved side effect profile, particularly a reduced tendency to cause nausea, vomiting, sedation and respiratory depression.

About CeNeS short-acting sedative programme

A series of short-acting sedatives were assigned to CeNeS from GlaxoSmithKline (GSK) in November 2003. Building on the experience gained with the short-acting opiate, remifentanil, these compounds were developed by GSK to improve upon the widely-used sedative, midazolam.

The lead compound, CNS 7056X, is an ester that is rapidly hydrolysed in the body by esterases to an inactive metabolite. An attractive potential advantage offered by this mechanism of deactivation is a more predictable onset and offset profile compared to that seen with midazolam. Pre-clinical studies reveal that CNS 7056X has a significantly shorter duration of action than midazolam. The lack of reliance on a cytochrome P450 system for metabolism also means less scope for drug-drug interactions than midazolam. CNS 7056X is currently in pre-clinical development.
 

- In a talk at the European Society for Intravenous Anaesthesia (EuroSIVA, Vienna, Austria 27th-28th May 2005, entitled ‘New Drugs for Hypnosis and Sedation’ CeNeS’ Director of Drug Discovery, Dr Gavin Kilpatrick, gave the first public presentation of data on CeNeS’ novel short-acting sedatives.
 

www.cenes.com

 
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For more information please contact:

CeNeS Pharmaceuticals plc Neil Clark Tel: +44 (0)1223 266466

Northbank Communications Emma Palmer Douglas Pretsell Rowan Minnion Tel: +44 (0)20 7886 8150

About CeNeS Pharmaceuticals CeNeS is a biopharmaceutical company specialising in the development and commercialisation of drugs for pain control, sedation and other CNS disorders such as Parkinson’s disease. The company is based in Cambridge, England. For further information visit the CeNeS web site: www.cenes.com


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