Document Detail


Anesthetic profile of dexmedetomidine identified by stimulus-response and continuous measurements in rats.
MedLine Citation:
PMID:  10490899     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
C J Bol; J P Vogelaar; J W Mandema
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  291     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-10-12     Completed Date:  1999-10-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  153-60     Citation Subset:  IM    
Affiliation:
Department of Anesthesia and Pharmacology, Stanford University School of Medicine, Stanford, California. kbol@janbe.jnj.com
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MeSH Terms
Descriptor/Qualifier:
Analgesics, Non-Narcotic / pharmacokinetics,  pharmacology*
Animals
Cardiovascular System / drug effects
Electroencephalography / drug effects
Heart Rate / drug effects
Imidazoles / pharmacokinetics,  pharmacology*
Male
Medetomidine
Pain Measurement
Rats
Rats, Wistar
Grant Support
ID/Acronym/Agency:
GM-51309/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 0/Imidazoles; 86347-14-0/Medetomidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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