Aim of the study: Parkinson’s disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms.
Materials and methods: The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot.
Results: In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.
Conclusions: These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway. 相似文献
SummaryThe analgesic potency of nefopam was compared to that of morphine, pentazocine and pethidine, double-blind in 200 patients with post-operative pain. Each drug was given as a single intramuscular injecton on the first post-operative day. Pain relief was measured both with a 0 to 3 graded pain scale and a 0 to 10 visual analogue scale and expressed as pain intensity, pain intensity difference and sum of pain intensity difference. The degree and time course of pain relief was similar for all four treatments with maximum analgesia 90 minutes after injection. Side-effects were reported by 58% of patients on nefopam compared to 68% on morphine, 82% on pentazocine and 74% on pethidine, the commonest side-effect being sleepiness. These results suggest that nefopam is a sufficiently potent analgesic agent to control post-operative pain, with a relatively low incidence of side-effects. 相似文献
Epidural morphine in patient-controlled analgesia regimens controls postoperative pain well but easily induces pruritus and other epidural morphine-related side effects. With 90 pregnant American Society of Anesthesiologists physical status II females scheduled for elective cesarean delivery, the present study was designed to evaluate the efficacy and safety profile of patient-controlled antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation of postoperative pruritus and related side effects in combination with epidural morphine patient-controlled analgesia with regard to the quality of postoperative pain management. Patients were randomly assigned to two nalbuphine groups (5 μg/kg/hour, Group N5 or 10 μg/kg/hour, Group N10) and bolus dose of 1.6 μg/kg for PCP or the control (normal saline) group. Comparable visual analog scale scores for rest pain at each measured time interval among the three groups demonstrated that adequate pain relief was offered; however, the cumulative dose of nalbuphine administered to the patients in Group N10 attenuated the analgesic effect of epidural morphine in moving pain at POh24 only. Fewer episodes and milder severity of pruritus were observed in patients in Groups N5 and N10 at all postoperative time intervals. Epidural morphine provided good postoperative pain relief but with incommodious side effects. In addition, intravenous nalbuphine not only attenuated the incidence of pruritus but also decreased total morphine consumption. In conclusion, intravenous administration of low-dose nalbuphine (5 μg/kg/hour) for PCP maintained analgesia produced by epidural morphine and offered low pruritus incidence. 相似文献
Background: US FDA guidance recommends measuring the degree of effort needed to manipulate abuse-deterrent (AD) opioids. The ALERRT® instrument (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor, effort, and resources necessary to physically compromise AD product candidates in standardized settings. Objective: Use the ALERRT® instrument for testing morphine abuse-deterrent, extended-release, injection-molded tablets (ADER-IMT) 60 and 100 mg and the comparators immediate-release (IR) morphine sulfate 30 mg and extended-release (ER) morphine sulfate 60 mg. Methods: Four technicians tested the products using 10 household tools. The ALERRT instrument quantified effort (all tools) and time (3 preselected tools) required for manipulation. Results: Morphine-ADER-IMT 60 and 100 mg were difficult to manipulate, as demonstrated by high scores (mean range, 71.0?99.0 and 77.0?99.5, respectively). IR and ER morphine sulfate were easy to manipulate (low scores; mean range, 2.0?14.8 and 2.3?17.5, respectively). Statistically significant mean differences between morphine-ADER-IMT and comparators’ ALERRT scores were observed. Manipulations of morphine-ADER-IMT 60 and 100 mg for 300 seconds failed to produce substantial powdering. Manipulations of IR morphine sulfate (mean range, 65.5?175.8 seconds) and ER morphine sulfate (49.3?163.0 seconds) produced substantial to complete powdering in 92% of tablets. Conclusions: Morphine-ADER-IMT was extremely difficult to manipulate versus non-AD formulations of morphine. The ALERRT system differentiated the degree of effort for manipulation of morphine-ADER-IMT and non-AD morphine formulations, indicating sensitivity of this instrument as part of Category 1 testing. By measuring the degree of effort required for manipulation, the ALERRT instrument provides an empirical assessment into the relative difficulty of manipulating opioid analgesics for abuse. 相似文献