A recent study published in Current Molecular Pharmacology reveals that Coenzyme Q2 (CoQ2), a synthetic analog of ubiquinone, exhibits sedative-hypnotic properties in mice. The research, led by Dr. Richard J. Levy and colleagues at Columbia University Irving Medical Center, demonstrates that CoQ2 induces reversible loss of righting reflex and alters electroencephalogram activity, confirming its anesthetic potential.
Like its relative CoQ1, CoQ2 disrupts mitochondrial membrane potential by inducing excessive proton leak and inhibiting electron transport chain complexes I and IV. However, CoQ2 shows distinct pharmacokinetics: “We observed a delayed onset of hypnosis and a longer duration of unconsciousness compared to CoQ1, likely due to its longer isoprenoid tail,” said Dr. Levy.
The study also found that the source of proton leak differs between the two analogs. While CoQ1 acts through the mitochondrial carrier Aralar, CoQ2-induced leak is independent of Aralar and can be blocked by the non-specific inhibitor p-hydroxymercuribenzoate. “This suggests that side-chain length influences not only anesthetic potency but also the specific mitochondrial pathways engaged,” Dr. Levy added.
These findings position benzoquinones as a promising subclass of anesthetics and highlight mitochondria as critical targets for future anesthetic development.
Current Molecular Pharmacology