Advances in the development of novel analgesics

Background: Chronic pain conditions, whether inflammatory or neuropathic in origin remain a significant unmet medical need. Existing treatments exhibit insufficient efficacy and also produce dose-limiting side effects. As such, research is focused on identifying new drugs with novel mechanisms of action to better serve patient needs. Objectives: This review focuses on the most recent chemical scaffolds that are being investigated towards advancing selective small molecule cannabinoid agonists (CB2), ion channel modulators (sodium channels, calcium channels, potassium channels, transient receptor potential channels, acid-sensing ion channels and purinergic receptors) as well as modulators of the norepinephrine system into the clinic. Methods: We systematically searched, analyzed and summarized the publication and patent literature for small molecule inhibitors of the topic areas within the period January 2007 - February 2008. Information on clinical candidates, when available, was garnered from company websites and commercial databases. Conclusions: Our analysis reveals prolific patenting activity in the pain area associated with the chosen targets. As our targets are only a subset of those under investigation for pain, this therapeutic area seems to be a focus in both academic institutions and industry. Brain penetration and selectivity emerge as likely prerequisites for avoidance of adverse events and to achieve meaningful clinical efficacy.