Melatonin and anesthesia: a clinical perspective

The hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a novel hypnotic-anesthetic agent. Sublingually or orally administered melatonin is an effective premedicant in adults and children. Melatonin premedication like midazolam is associated with sedation and preoperative anxiolysis, however, unlike midazolam these effects are not associated with impaired psychomotor skills or the quality of recovery. Melatonin administration also is associated with a tendency toward faster recovery and a lower incidence of postoperative excitement than midazolam. Oral premedication with 0.2 mg/kg melatonin significantly reduces the propofol and thiopental doses required for loss of responses to verbal commands and eyelash stimulation. In rats, melatonin and the more potent melatonin analogs 2-bromomelatonin and phenylmelatonin have been found to have anesthetic properties similar to those of thiopental and propofol, with the added advantage of providing potent antinociceptive effects. The exact mechanism(s) by which structurally diverse intravenous and volatile anesthetics produce general anesthesia is still largely unknown, but positive modulation of gamma-aminobutyric acid type A (GABA(A)) receptor function has been recognized as an important and common pathway underlying the depressant effects of many of these agents. Accumulating evidence indicates that there is interplay between the melatonergic and GABAergic systems, and it has been demonstrated that melatonin administration produces significant, dose-dependent increases in GABA concentrations in the central nervous system. Additional in vitro data suggest that melatonin alters GABAergic transmission by modulating GABA(A) receptor function. Of greater importance, data from in vivo studies suggest that the central anesthetic effects of melatonin are mediated, at least in part, via GABAergic system activation, as they can be blocked or reversed by GABA(A) receptor antagonists. Further work is needed to better understand the general anesthetic properties of melatonin at the molecular, cellular, and systems levels.