4-isopropylcyclohexanol has potential analgesic effects through the inhibition of anoctamin 1, TRPV1 and TRPA1 channel activities.

Abstract

Interactions between calcium-activated chloride channel anoctamin 1 (ANO1) and transient receptor potential vanilloid 1 (TRPV1) enhance pain sensations in mice, suggesting that ANO1 inhibition could have analgesic effects. Here we show that menthol and the menthol analogue isopropylcyclohexane (iPr-CyH) inhibited ANO1 channels in mice. The iPr-CyH derivative 4-isopropylcyclohexanol (4-iPr-CyH-OH) inhibited mouse ANO1 currents more potently than iPr-CyH. Moreover, 4-iPr-CyH-OH inhibited the activities of TRPV1, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8) and TRPV4. Single-channel analysis revealed that 4-iPr-CyH-OH reduced TRPV1 and TRPA1 current open-times without affecting unitary amplitude or closed-time, suggesting that it affected gating rather than blocking the channel pore. The ability of 4-iPr-CyH-OH to inhibit action potential generation and reduce pain-related behaviors induced by capsaicin in mice suggests that 4-iPr-CyH-OH could have analgesic applications. Thus, 4-iPr-CyH-OH is a promising base chemical to develop novel analgesics that target ANO1 and TRP channels.

• Authors: Yasunori Takayama, Hidemasa Furue, Makoto Tominaga
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 43132 (02 22 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28225032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Anoctamin-1
• Cyclohexanols
• TRPA1 Cation Channel
• TRPV Cation Channels
• TRPV1 protein, mouse
• Trpa1 protein, mouse
• 4-isopropylcyclohexanol
• Capsaicin

Topics

• Action Potentials
• Analgesics (pharmacology)
• Animals
• Anoctamin-1 (antagonists & inhibitors)
• Capsaicin (metabolism)
• Cyclohexanols (pharmacology)
• Mice, Inbred C57BL
• TRPA1 Cation Channel (antagonists & inhibitors)
• TRPV Cation Channels (antagonists & inhibitors)