This study investigated the effects of increasing plasma concentrations of dexmedetomidine in healthy human subjects. Ten male volunteers (aged 20-27 years) were monitored during sequential 40-minute intravenous infusions of dexmedetomidine at target concentrations of 0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml. The study measured hemodynamic parameters, blood sampling, and psychometric, cold pressor, and baroreflex tests at rest and during the infusions. Key findings include: - Initial doses of dexmedetomidine decreased catecholamines by 45-76% and eliminated norepinephrine increases during the cold pressor test. - Catecholamine suppression persisted with subsequent infusions. - The first two doses increased sedation by 38% and 65%, and mean arterial pressure by 13%, but did not change central venous or pulmonary artery pressures. - Higher doses increased sedation, all pressures, and vascular resistance, leading to significant decreases in heart rate, cardiac output, and stroke volume. - Memory recall and recognition decreased at doses above 0.7 ng/ml. - Pain ratings and mean arterial pressure increases during the cold pressor test diminished with increasing dexmedetomidine doses. - Baroreflex heart rate slowing was potentiated at both doses of dexmedetomidine. - Respiratory variables were minimally changed, and acid-base status remained stable. The study concluded that increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic dose-response relationship was observed for mean arterial pressure, pulmonary arterial pressure, and vascular resistances, and the cold pressor response was attenuated.This study investigated the effects of increasing plasma concentrations of dexmedetomidine in healthy human subjects. Ten male volunteers (aged 20-27 years) were monitored during sequential 40-minute intravenous infusions of dexmedetomidine at target concentrations of 0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml. The study measured hemodynamic parameters, blood sampling, and psychometric, cold pressor, and baroreflex tests at rest and during the infusions. Key findings include: - Initial doses of dexmedetomidine decreased catecholamines by 45-76% and eliminated norepinephrine increases during the cold pressor test. - Catecholamine suppression persisted with subsequent infusions. - The first two doses increased sedation by 38% and 65%, and mean arterial pressure by 13%, but did not change central venous or pulmonary artery pressures. - Higher doses increased sedation, all pressures, and vascular resistance, leading to significant decreases in heart rate, cardiac output, and stroke volume. - Memory recall and recognition decreased at doses above 0.7 ng/ml. - Pain ratings and mean arterial pressure increases during the cold pressor test diminished with increasing dexmedetomidine doses. - Baroreflex heart rate slowing was potentiated at both doses of dexmedetomidine. - Respiratory variables were minimally changed, and acid-base status remained stable. The study concluded that increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic dose-response relationship was observed for mean arterial pressure, pulmonary arterial pressure, and vascular resistances, and the cold pressor response was attenuated.