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Respir Physiol Neurobiol. 2013 Oct 1;189(1):136-43. doi: 10.1016/j.resp.2013.07.007. Epub 2013 Jul 23.

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

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Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.


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.


Arterial blood–gas chemistry; Halothane-anesthetized rats; Morphine; l-Cysteine ethylester

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