Present address: BMS–In Vivo Biology, Syngene International Ltd., Bangalore, India.
The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1
Article first published online: 17 FEB 2009
© 2009 The Authors. Journal compilation © 2009 The British Pharmacological Society
British Journal of Pharmacology
Volume 156, Issue 3, pages 412–419, February 2009
How to Cite
Fowler, C., Naidu, P., Lichtman, A. and Onnis, V. (2009), The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1. British Journal of Pharmacology, 156: 412–419. doi: 10.1111/j.1476-5381.2008.00029.x
This review is dedicated to the memory of J Michael Walker, a pioneer in the field of endocannabinoid pain research.
The British Journal of Pharmacology has previously published themed issues on Cannabinoid Pharmacology (2007) http://www3.interscience.wiley.com/journal/121667860/issue and CB2 Receptors (2008) http://www3.interscience.wiley.com/journal/121667727/issue.
- Issue published online: 17 FEB 2009
- Article first published online: 17 FEB 2009
- Received 1 July 2008; revised 19 August 2008; accepted 22 August 2008
- fatty acid amide hydrolase;
- non-steroidal anti-inflammatory drugs;
- transient receptor potential vanilloid type 1;
- inflammatory pain
Mandarin translation of abstract
Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs.