Microtubule-Stabilizer Epothilone B Delays Anesthetic-Induced Unconsciousness in Rats

• DOI: 10.1523/eneuro.0291-24.2024
• Publication Date: 2024-08-15T17:45:16Z
• Authors: Sana Khan; Yixiang Huang; Derin Timuçin; Shantelle Bailey; Sophia Lee; Jessica Lopes; Emeline Gaunce; Jasmine Mosberger; Michelle Zhan; Bothina Abdelrahman; Xiran Zeng; Michael C. Wiest
• Keywords: Unconsciousness

Volatile anesthetics are currently believed to cause unconsciousness by acting on one or more molecular targets including neural ion channels, receptors, mitochondria, synaptic proteins, and cytoskeletal proteins. Anesthetic gases isoflurane bind microtubules (MTs) dampen their quantum optical effects, potentially contributing causing unconsciousness. This possibility is supported the finding that taxane chemotherapy consisting of MT-stabilizing drugs reduces effectiveness anesthesia during surgery in human cancer patients. In order experimentally assess contribution MTs as functionally relevant volatile anesthetics, we measured latencies loss righting reflex (LORR) under 4% male rats injected subcutaneously with vehicle 0.75 mg/kg brain-penetrant drug epothilone B (epoB). EpoB-treated took an average 69 s longer become unconscious latency LORR. was a statistically significant difference corresponding standardized mean (Cohen's