Friday, May 05, 2006

Acetaminophen - the future of multiple sclerosis & Parkinson's disease therapy?

DailyUpdates May 5th, 2006: The pick of oday's edition of DailyUpdates (see it in full here) provides data to suggest that the long sought after mechanism to explain the analgesic properties of acetaminophen may involve the cannabinoid pathway. But, could these data open up the utility of a therapeutic agent in existence for over 100 years to include the treatment of neurodegenerative disorders such as multiple sclerosis and Parkinson's disease?

Acetaminophen: A new mechanism of action involving the cannabinoid pathway may widen its utility to neurodegenerative disorders? The market for over the counter pain medications is massive (see for example The US Market for OTC Pain Medication). Acetaminophen, commonly referred to by its brand names Tylenol and Paracetamol, is often the first drug used for control of mild to moderate pain especially when aspirin is contraindicated. Although acetaminophen has been used as an analgesic for well over 100 years its mechanism of action is unclear. Today's featured article reports data using the hot plate assay suggesting that the analgesic effect of paracetamol is prevented by cannabinoid CB1 receptor antagonism. This study suggests that acetaminophen somehow activates the cannabinoid pathway and this is consistent with a second recent study (Hoggestat et al, 2005) reporting that acetaminophen, following deacetylation to its primary amine, is conjugated with arachidonic acid in the brain and the spinal cord to form the N-arachidonoylphenolamine (AM404). This molecule in turn is well known as an endocannabinoid reuptake inhibitor; in other words acetaminophen may exert analgesic effects through the amplification of endogenous cannabioid pathways. Considering the blockbuster potential and multiple indications of cannabinoid therapeutics (see Cannabinoids - A potential blockbuster market), based on these two studies the benefit of paracetamol or molecules modelled on its chemical structure may extend past one of analgesia. Of note CB1 receptor activation may be of interest for the treatment of multiple sclerosis or Parkinson's disease. Since acetaminophen appears to be converted to AM404 in the brain an intriguing possibility arises that paracetamol may increase CB1 receptor activation by preventing cannabinoid metabolism in a highly selective fashion in the brain circumventing problems associated with nonselective cannabinoid receptor activation in the periphery. Could acetaminophen or its analogues represent a new approach to neurodegenerative disorders? Feel free to post your comments on our Drug Discovery Forum

Breaking News - Neurobiological Technologies's stroke treatment, Viprinex, moves closer to the market : Stroke is one of the top three causes of death and incidence is expected to increase in the next ten years. Long term disability caused by stroke is a major economic burden on healthcare systems, current treatment options are limited and general awareness of stroke is poor. Therefore the opportunity for new drugs is huge and lucrative for companies willing to invest in increasing awareness (for a full evaluation of this field see our feature Acute Stroke) One company highly involved in this arena is Neurobiological Technologies who have just announced the initiation of its second Phase III study of Viprinex (Ancrod) in patients with acute ischemic stroke. Clinical data suggest that Viprinex is a powerful defibrinogenating agent causing enhanced blood flow, a fibrinolytic agent, as well as an anticoagulant helping to limit stroke extension.


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