Pharmacological effects of medetomidine in humans

Single i.v. doses of medetomidine have been administered to healthy male volunteers in three clinical phase I studies. After an initial open dose-finding study, double-blind, placebocontrolled designs were used. The highest dose tested was 120 micrograms. Medetomidine was well tolerated. It caused dose-dependent decreases of blood pressure (max 22/14 mmHg), heart rate (max 14/min) and cardiac output (max 21%) without subjective sensations of hemodynamic changes or other unexpected side-effects. However, a clear dose-dependent sedative effect, both subjective and objective, and a decrease in salivation was seen after single i.v. doses. Medetomidine had a powerful and dose-dependent effect in reducing noradrenaline (by a maximum of 75%) and increasing human growth hormone levels in plasma. All the observed pharmacological effects are well compatible with an alpha 2-agonistic action of the drug and resemble those seen after i.v. administration of clonidine. However, medetomidine appeared to be more potent and short-acting than clonidine.