Anesthetic Profile of Dexmedetomidine Identified by Stimulus-Response and Continuous Measurements in Rats

• Published in: The Journal of pharmacology and experimental therapeutics 1999-10, Vol.291 (1), p.153-160
• Main Authors: Bol, C J, Vogelaar, J P, Mandema, J W
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - pharmacokinetics; Analgesics, Non-Narcotic - pharmacology; Animals; Cardiovascular System - drug effects; Electroencephalography - drug effects; Heart Rate - drug effects; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Male; Medetomidine; Pain Measurement; Rats; Rats, Wistar
• ISSN: 0022-3565; 1521-0103

This study characterizes the anesthetic profile of dexmedetomidine on the basis of steady-state plasma concentrations using defined stimulus-response, ventilatory, and continuous electroencephalographic (EEG) and cardiovascular effect measures in rats. At constant plasma concentrations of dexmedetomidine (range, 0.5–19 ng/ml), targeted and maintained by target-controlled infusion, the whisker reflex, righting reflex, startle reflex (to noise), tail clamp response, hot water tail-flick latency, and attenuation of heart rate (HR) increase associated with tail-flick (sympathoadrenal block) and corneal reflex, were assessed in 22 rats. EEG (power in 0.5- to 3.5-Hz frequency band), mean arterial pressure, and HR were recorded continuously. Blood gas values and arterial drug concentrations were determined regularly. The following steady-state plasma EC 50 values of dexmedetomidine (mean ± S.E. nanograms per milliter) were estimated: HR decrease (0.51 ± 0.04), EEG (1.02 ± 0.08), whisker reflex (1.09 ± 0.10), sympathoadrenal block (1.85 ± 0.80), mean arterial blood pressure increase (1.99 ± 0.44), righting reflex (2.13 ± 0.15), tail-flick latency (3.65 ± 0.87), startle reflex (3.75 ± 0.64), tail clamp (5.49 ± 1.34), and corneal reflex (24.5 ± 12.3). At the EC 50 value of tail clamp, ventilatory depression was minor. In rats, dexmedetomidine creates bradycardia, sedation/hypnosis, sympathoadrenal blocking effects, and blood pressure-increasing effects at plasma concentrations below 2.5 ng/ml. Higher plasma concentrations are needed to loose the startle reflex, tail-flick, tail clamp, and corneal reflex responses. Ventilatory depressant effects are minor. The applied EEG measure seems to reflect sedation/hypnosis but seems to have limited value to predict the deeper levels of analgesia and anesthesia of dexmedetomidine.