Chronic pain can result from various disease conditions and about 45% of the U. S. population seeks medical help for treatment of pain. Neuropathic pain is a type of chronic pain which is very difficult to treat, and most patients do not get adequate relief. A promising therapeutic drug target for the treatment of inflammation and pain is the cannabinoid CB2 receptor. In Phase I of this proposal our focus will be on the structural optimization of our lead template to develop a high efficacy CB2 selective agonist with pain suppression potential and with no CNS side effects. Established in vivo and in vitro pharmacological assays will be used to identify compounds that: 1) are highly selective for CB2 over CB1 receptors;2) possess high efficacy and high potency in binding and activating the CB2 receptor;3) possess high efficacy in reversing allodynia (i.e., nociceptive behavior in response to normally non-noxious stimuli);and 4) lack cannabimimetic side effects in whole animals that are typically indicative of CB1 receptor activation. The long-term objective of this proposal is to develop a novel drug for treatment of chronic pain which is both safe and effective.
Neuropathic pain is a type of chronic pain which is very difficult to treat since most patients do not get adequate relief with existing medications. The goal of this proposal is to develop CB2 receptor agonists with limited or no CNS side effects for the treatment of chronic pain.