HCN channels constitute an attractive target for treating chronic pain. Analgesics targeting HCN1 must spare the cardiac pacemaker current, which is carried mostly by HCN2 and HCN4. The general anesthetic propofol selectively inhibits HCN1 channels versus HCN2–4. As a consequence, it was hypothesized that propofol and congeners should be antihyperalgesic. 2,6-Di-tert-butylphenol (2,6-DTBP) is more potent than propofol for HCN1 while maintaining selectivity over HCN2–4. In a peripheral nerve ligation model of neuropathic pain, 2,6-DTBP and subhypnotic propofol are anthyperalgesic. The findings are consistent with these compounds exerting analgesia via the HCN1 channel.
See article at J Pharmacol Exp Ther 2013, 345:363–373.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics