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L-Cysteine ethyl ester reverses the deleterious effects of morphine on, arterial blood-gas chemistry in tracheotomized rats.

Abstract
This study determined whether the membrane-permeable ventilatory stimulant, L-cysteine ethylester (L-CYSee), reversed the deleterious actions of morphine on arterial blood-gas chemistry in isoflurane-anesthetized rats. Morphine (2 mg/kg, i.v.) elicited sustained decreases in arterial blood pH, pO₂ and sO₂, and increases in pCO₂ (all responses indicative of hypoventilation) and alveolar-arterial gradient (indicative of ventilation-perfusion mismatch). Injections of L-CYSee (100 μmol/kg, i.v.) reversed the effects of morphine in tracheotomized rats but were minimally active in non-tracheotomized rats. L-cysteine or L-serine ethylester (100 μmol/kg, i.v.) were without effect. It is evident that L-CYSee can reverse the negative effects of morphine on arterial blood-gas chemistry and alveolar-arterial gradient but that this positive activity is negated by increases in upper-airway resistance. Since L-cysteine and L-serine ethylester were ineffective, it is evident that cell penetrability and the sulfur moiety of L-CYSee are essential for activity. Due to its ready penetrability into the lungs, chest wall muscle and brain, the effects of L-CYSee on morphine-induced changes in arterial blood-gas chemistry are likely to involve both central and peripheral sites of action.
AuthorsJames Mendoza, Rachael Passafaro, Santhosh Baby, Alex P Young, James N Bates, Benjamin Gaston, Stephen J Lewis
JournalRespiratory physiology & neurobiology (Respir Physiol Neurobiol) Vol. 189 Issue 1 Pg. 136-43 (Oct 01 2013) ISSN: 1878-1519 [Electronic] Netherlands
PMID23892097 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Narcotics
  • Carbon Dioxide
  • ethyl cysteine
  • Morphine
  • Cysteine
  • Oxygen
Topics
  • Animals
  • Blood Gas Analysis
  • Carbon Dioxide (blood)
  • Cysteine (analogs & derivatives, pharmacology)
  • Hydrogen-Ion Concentration
  • Male
  • Morphine (adverse effects)
  • Narcotics (adverse effects)
  • Oxygen (blood)
  • Pulmonary Gas Exchange (drug effects)
  • Pulmonary Ventilation (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Tracheotomy

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