Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats

J Pharmacol Exp Ther. 1999 Oct;291(1):153-60.

Abstract

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 milliliter) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • Analgesics, Non-Narcotic
  • Imidazoles
  • Medetomidine