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In addition, we do not know whether co-injections of L-NAC or L-NACme alter the antinociception actions of fentanyl (e.g., analgesia, expected tolerance, and occurrence of hyperalgesia), although we have reported that (a) bolus injections of L-NAC do not impair analgesia induced by continuous infusion of fentanyl in rats, despite reversing fentanyl-induced OIRD 20 , and (b) bolus injections of other L-D-thiolesters, such as D-cysteine di(m)ethyl ester, L- or D-cysteine (m)ethyl esters, and L-glutathione ethyl ester, prevent/overcome the actions of fentanyl and morphine on ventilatory parameters, and arterial blood-gas chemistry in rats without compromising opioid-induced analgesia or sedation 36

This has been indicated in the ADAGIO and TEMPO trials with selegiline administration, especially with early compared to late administration, which can reduce the intensity of PD symptoms such as gait, postural instability, tremors, and bradykinesia [33]

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