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.