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N-Methyl-D-Aspartate (NMDA) Antagonists-S(+)-ketamine, Dextrorphan, and Dextromethorphan-Act as Calcium Antagonists on Bovine Cerebral Arteries

Kamel, Ihab R.; Wendling, Woodrow W.; Chen, Dong; Wendling, Karen S.; Harakal, Concetta and Carlsson, Christer L LU (2008) In Journal of Neurosurgical Anesthesiology 20(4). p.241-248
Abstract
Ketamine an intravenous anesthetic and a major drug of abuse, is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Ketamine's enantiomer. S(+)-ketamine, acts stereoselectively on neuronal NMDA receptors. The purpose of this in vitro study was to compare the direct effects of S(+)-ketamine. 2 other noncompetitive NMDA receptor antagonists (dextrorphan and dextromethorphan), and the calcium entry blocker nimodipine on the cerebral vasculature, using bovine middle cerebral arterics as an experimental model. Arterial rings were mounted in isolated tissue chambers equipped with isometric tension transducers to obtain pharmacologic dose-response curves. In the absence of exogenous vasoconstrictor, the NMDA antagonists or... (More)
Ketamine an intravenous anesthetic and a major drug of abuse, is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Ketamine's enantiomer. S(+)-ketamine, acts stereoselectively on neuronal NMDA receptors. The purpose of this in vitro study was to compare the direct effects of S(+)-ketamine. 2 other noncompetitive NMDA receptor antagonists (dextrorphan and dextromethorphan), and the calcium entry blocker nimodipine on the cerebral vasculature, using bovine middle cerebral arterics as an experimental model. Arterial rings were mounted in isolated tissue chambers equipped with isometric tension transducers to obtain pharmacologic dose-response curves. In the absence of exogenous vasoconstrictor, the NMDA antagonists or nimodipine had negligible effects oil cerebral arterial tone. When rings were preconstricted with either potassium or the stable thromboxane A(2) mimetic U46619. the NMDA antagonists and nimodipine each produced dose-dependent relaxation. Prior endothelial stripping had no effect on subsequent drug-induced relaxation of K+-constricted rings. In Ca2+-deficient media containing either potassium or U46619. the NMDA antagonists and nimodipine each produced competitive inhibition of subsequent Ca2+ induced constriction. In additional experiments, arterial strips were mounted in isolated tissue chambers to directly measure calcium uptake, using (45)calcium (Ca-45) as a radioactive tracer. The NMDA antagonists and nimodipine each blocked potasium-stimulated or U46619-stilmulated Ca-45 uptake into arterial strips. These results indicate that S(+)-ketamine, dextrorphan, arteries by acting as calcium antagonists; they all inhibit Ca-45 uptake through both potential-operated (potassium) and receptor-operated (U46619) channels in cerebrovascular smooth muscle. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
calcium channel, L-type, nimodipine, dextromethorphan, S(+)-ketamine, dextrorphan, vascular smooth muscle, cattle
in
Journal of Neurosurgical Anesthesiology
volume
20
issue
4
pages
241 - 248
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000260069700004
  • scopus:58949098904
ISSN
1537-1921
language
English
LU publication?
yes
id
7c94c369-d67c-4bba-8064-fbddc50eccca (old id 1284628)
alternative location
http://www.jnsa.com/pt/re/jneurosurganes/abstract.00008506-200810000-00004.htm
date added to LUP
2009-02-09 09:46:24
date last changed
2017-11-05 03:59:07
@article{7c94c369-d67c-4bba-8064-fbddc50eccca,
  abstract     = {Ketamine an intravenous anesthetic and a major drug of abuse, is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Ketamine's enantiomer. S(+)-ketamine, acts stereoselectively on neuronal NMDA receptors. The purpose of this in vitro study was to compare the direct effects of S(+)-ketamine. 2 other noncompetitive NMDA receptor antagonists (dextrorphan and dextromethorphan), and the calcium entry blocker nimodipine on the cerebral vasculature, using bovine middle cerebral arterics as an experimental model. Arterial rings were mounted in isolated tissue chambers equipped with isometric tension transducers to obtain pharmacologic dose-response curves. In the absence of exogenous vasoconstrictor, the NMDA antagonists or nimodipine had negligible effects oil cerebral arterial tone. When rings were preconstricted with either potassium or the stable thromboxane A(2) mimetic U46619. the NMDA antagonists and nimodipine each produced dose-dependent relaxation. Prior endothelial stripping had no effect on subsequent drug-induced relaxation of K+-constricted rings. In Ca2+-deficient media containing either potassium or U46619. the NMDA antagonists and nimodipine each produced competitive inhibition of subsequent Ca2+ induced constriction. In additional experiments, arterial strips were mounted in isolated tissue chambers to directly measure calcium uptake, using (45)calcium (Ca-45) as a radioactive tracer. The NMDA antagonists and nimodipine each blocked potasium-stimulated or U46619-stilmulated Ca-45 uptake into arterial strips. These results indicate that S(+)-ketamine, dextrorphan, arteries by acting as calcium antagonists; they all inhibit Ca-45 uptake through both potential-operated (potassium) and receptor-operated (U46619) channels in cerebrovascular smooth muscle.},
  author       = {Kamel, Ihab R. and Wendling, Woodrow W. and Chen, Dong and Wendling, Karen S. and Harakal, Concetta and Carlsson, Christer L},
  issn         = {1537-1921},
  keyword      = {calcium channel,L-type,nimodipine,dextromethorphan,S(+)-ketamine,dextrorphan,vascular smooth muscle,cattle},
  language     = {eng},
  number       = {4},
  pages        = {241--248},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Neurosurgical Anesthesiology},
  title        = {N-Methyl-D-Aspartate (NMDA) Antagonists-S(+)-ketamine, Dextrorphan, and Dextromethorphan-Act as Calcium Antagonists on Bovine Cerebral Arteries},
  volume       = {20},
  year         = {2008},
}