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The alpha2-receptor agonist, dexmedetomidine, provides sedation with facilitated arousal and analgesia with no respiratory depression. These properties render it potentially useful for anesthesia premedication, although parenteral administration is not practical in this setting. We designed this study to evaluate the sedative, anxiolytic, analgesic, and hemodynamic effects of dexmedetomidine administered intranasally in healthy volunteers.Koch's design for crossover trials (three-treatment and two-period design) was adopted. The study was double-blind and there were three treatment groups: A (placebo), B (intranasal dexmedetomidine 1 μg/kg) and C (intranasal dexmedetomidine 1.5 μg/kg). Each of the 18 subjects participated in two study periods. The study drug was administered intranasally after baseline observations of modified Observer Assessment of Alertness/Sedation Scale, visual analog scale of sedation, bispectral index, visual analog scale of anxiety, pain pressure threshold measured by an electronic algometer, systolic blood pressure (SBP) and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation. These were repeated during the course of the study.Intranasal dexmedetomidine was well tolerated. Both 1 and 1.5 μg/kg doses equally produced significant sedation and decreases in bispectral index, SBP, diastolic blood pressure, and heart rate when compared with placebo (P < 0.05). The onset of sedation occurred at 45 min with a peak effect at 90–150 min. The maximum reduction in SBP was 6%, 23%, and 21% for Groups A, B, and C respectively. There was no effect on pain pressure threshold, oxygen saturation or respiratory rate. Anxiolysis could not be evaluated as no subjects were anxious at baseline.The intranasal route is effective, well tolerated, and convenient for the administration of dexmedetomidine. Future studies are required to evaluate the possible role of the noninvasive route of administration of dexmedetomidine in various clinical settings, including its role as premedication prior to induction of anesthesia.