• Kazuko Taiji.
• Development & Regulatory, Therapeutic Group 1, Abbott Japan Co., Ltd. Kazuko.Taiji@abbott.com
• Nippon Yakurigaku Zasshi. 2004 Sep 1;124(3):171-9.

AbstractDexmedetomidine hydrochloride (Precedex) is a potent and highly selective central alpha(2)-adrenoreceptor agonist. In a test of affinity to receptors in rat brain cortex, this drug showed a high affinity and selectivity to the alpha(2)-adrenoreceptor. This drug induced a dose-dependent decrease in activity, loss of righting reflex, an increase in sedation score, and a dose-dependent prolongation of the latent time of escape from pain in various animal models. The site of action for the sedative action of this drug is considered to be the locus coeruleus. With administration of this drug into the locus coeruleus, loss of righting reflex was observed in almost all animals. Test results using mice with variant alpha(2A)-receptor suggested that the sedative action of this drug is expressed through the alpha(2A)-receptor subtype. This drug is promptly eliminated from blood. In the phase II/III multi-center placebo-controlled double blind bridging study conducted in Japan, efficacy and safety were examined in patients brought to the ICU. As regards sedative action, the ratio of patients who did not require additional propofol medication (>50 mg) while intubated was taken as the effective rate. The drug group showed a significantly high effective rate (90.9%; placebo group, 44.6%). Similarly, with analgesic action, the ratio of patients who did not require additional morphine medication during intubation was taken as the effective rate. The effective rate for the drug group was significantly high (87.3%; placebo group, 75.0%). The main adverse events observed in the drug group were hypertension and hypotension.

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