Serotonin syndrome is a
drug-related toxicity caused by excess
serotonin within the central nervous system. We recently encountered a case of
serotonin syndrome that developed in the early postoperative period that was successfully treated with intravenous
dexmedetomidine. Although the prescriptive literature has commonly recommended sedation with
benzodiazepines for controlling agitation in
serotonin syndrome, the effectiveness of
dexmedetomidine has also been reported in several clinical conditions. In the present study, we conducted a reverse translational experiment to compare the efficacy of
dexmedetomidine and
midazolam, at equi-
sedative doses, on serotonergic toxicity-like responses in rats. Animals were subcutaneously injected with 0.75 mg/kg
8-OH-DPAT, a full
5-HT1A agonist. 8-OH-DPAT-treated rats showed
serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature, which were completely inhibited by pretreatment with
WAY 100635, a selective
5-HT1A antagonist (n = 8).
Intramuscular injection of
midazolam (1.0 mg/kg) or
dexmedetomidine (0.01 mg/kg), which comparably induced observable signs of sedation, was tested in the present study. Concomitant treatment with
midazolam significantly attenuated the hyperlocomotion, but failed to affect traditional
serotonin syndrome behaviors and body temperature in 8-OH-DPAT-treated rats (n = 8). On the other hand, concomitant treatment with
dexmedetomidine significantly attenuated all of these parameters (n = 8). The present case and related reverse translational experiment demonstrate that
dexmedetomidine may be more beneficial for the treatment of
serotonin syndrome compared to the current recommended treatment with
benzodiazepines.