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, pO 2 and sO 2 , and increases in pCO 2 (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.