Anesthetic action of methyleugenol and other eugenol derivatives

A comparative study of four natural eugenol compounds found in the volatile oil fraction of Myristica fragans, namely eugenol (E), methyleugenol (ME), isoeugenol and methylisoeugenol, was carried out in mice. Using a mixture of saline + tween-80 to suspend the compounds and the intraperitoneal route, ME revealed to be the most active and the less toxic in inducing the loss of the righting reflex. ME was further compared with pentobarbital and with the synthetic E derivative, propanidid, using the intraperitoneal route in rats. ME anesthetized the rats more rapidly than pentobarbital; however, the duration of anesthesia was the same for both drugs. Propanidid was not active when injected through the intraperitoneal route. Rats under ME anesthesia could be more easily operated, showed less cyanosis, and recovered better than those under pentobarbital. When injected intravenously in rabbits, ME and propanidid showed equivalent anesthetic effects. Daily intraperitoneal injections of ME in rats and mice for up to 42 days, showed that the drug was not toxic and that the animals became more sensitive to the anesthetic action with repeating the injections. Similarly to pentobarbital, ME induced large amounts of slow wave activity in EEG of rats and did not change the total brain levels of dopamine, norepinephrine, and 5-hydroxytryptamine.