Batch dependent - please inquire should you have specific requirements.
Buffer
0.01M pH7.4 PBS
Preservative
None
Storage
Shipped at 4°C. Upon delivery aliquot and store at -20°C. Avoid freeze / thaw cycles.
Keywords
morphine; Morphia; Morphinum;
Citations
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Background
Morphine was the first alkaloid isolated from plant extracts and was later found to be a potent analgesic and sedative, far more effective than other opioids. Morphine is widely used to relieve pain in various diseases such as cancer due to its rapid onset and relief, which is achieved through direct action on the central nervous system. However, morphine also affects peripheral tissues, which can lead to secondary complications such as respiratory depression, immunosuppression, constipation, etc. Long-term use of morphine can also lead to drug dependence and tolerance. Physiological dependence is characterized by adaptive neuronal changes due to continued exposure to the drug, resulting in withdrawal symptoms such as anorexia, coughing, abdominal pain, diarrhea, and anxiety upon discontinuation of the drug or administration of an antagonist such as naloxone. Morphine-induced tolerance is due to a decreased response to the drug after repeated exposure to the drug and increasing the dose to achieve the same relief or effect as the previous minimum dose.
Figure 1. Introduction to morphine-related tolerance and dependence (Source: Badshah I, et al. 2023)
Morphine acts on opioid 7-transmembrane G protein-coupled receptors with extracellular amino and intracellular carboxyl structural domains. G protein receptors are distributed throughout the body and are found in the gastrointestinal and respiratory tracts as well as the nervous system. This is the reason why the use of morphine can cause adverse reactions. Receptor desensitization leads to morphine tolerance and dependence, which refers to a decreased response due to receptor internalization or decreased surface receptor activity after repeated use of morphine or its analogs. Acute doses of morphine reduce cyclic adenosine monophosphate (cAMP) by altering calcium and potassium ion channels, leading to hyperpolarization, whereas chronic use of morphine alters receptor trafficking, leading to a reduction in the number of available surface receptors, thereby promoting morphine tolerance. On the other hand, morphine may induce the formation of free radicals or reduce antioxidant defenses, thereby causing cellular damage, and long-term use of morphine may disrupt redox-balanced cellular homeostasis, but the extent of this depends on a variety of factors, including age, sex, dose, duration of use, and interactions with other drugs. In addition, molecular mechanisms associated with morphine tolerance and dependence include the role of NMDA receptors, the role of PPAR.
References
1. Badshah I, et al. Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives. Mol Cell Biochem. 2023 Jul 20.
2. Zhang XY, et al. Morphine: double-faced roles in the regulation of tumor development. Clin Transl Oncol. 2018 Jul;20(7):808-814.
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References
Molecular recognition of morphine and fentanyl by the human μ-opioid receptor
Cell
Authors: Zhuang Y, Wang Y, He B, He X, Zhou XE, Guo S, Rao Q, Yang J, Liu J, Zhou Q, Wang X, Liu M, Liu W, Jiang X, Yang D, Jiang H, Shen J, Melcher K, Chen H, Jiang Y, Cheng X, Wang MW, Xie X, Xu HE.
Morphine and fentanyl are among the most used opioid drugs that confer analgesia and unwanted side effects through both G protein and arrestin signaling pathways of μ-opioid receptor (μOR). Here, we report structures of the human μOR-G protein complexes bound to morphine and fentanyl, which uncover key differences in how they bind the receptor. We also report structures of μOR bound to TRV130, PZM21, and SR17018, which reveal preferential interactions of these agonists with TM3 side of the ligand-binding pocket rather than TM6/7 side. In contrast, morphine and fentanyl form dual interactions with both TM3 and TM6/7 regions. Mutations at the TM6/7 interface abolish arrestin recruitment of μOR promoted by morphine and fentanyl. Ligands designed to reduce TM6/7 interactions display preferential G protein signaling. Our results provide crucial insights into fentanyl recognition and signaling of μOR, which may facilitate rational design of next-generation analgesics.
Intrathecal Morphine versus Intrathecal Hydromorphone for Analgesia after Cesarean Delivery: A Randomized Clinical Trial
Anesthesiology
Authors: Sharpe EE, Molitor RJ, Arendt KW, Torbenson VE, Olsen DA, Johnson RL, Schroeder DR, Jacob AK, Niesen AD, Sviggum HP.
Background: Intrathecal opioids are routinely administered during spinal anesthesia for postcesarean analgesia. The effectiveness of intrathecal morphine for postcesarean analgesia is well established, and the use of intrathecal hydromorphone is growing. No prospective studies have compared the effectiveness of equipotent doses of intrathecal morphine versus intrathecal hydromorphone as part of a multimodal analgesic regimen for postcesarean analgesia. The authors hypothesized that intrathecal morphine would result in superior analgesia compared with intrathecal hydromorphone 24 h after delivery.
Methods: In this single-center, double-blinded, randomized trial, 138 parturients undergoing scheduled cesarean delivery were randomized to receive 150 μg of intrathecal morphine or 75 μg of intrathecal hydromorphone as part of a primary spinal anesthetic and multimodal analgesic regimen; 134 parturients were included in the analysis. The primary outcome was the numerical rating scale score for pain with movement 24 h after delivery. Static and dynamic pain scores, nausea, pruritus, degree of sedation, and patient satisfaction were assessed every 6 h for 36 h postpartum. Total opioid consumption was recorded.
Results: There was no significant difference in pain scores with movement at 24 h (intrathecal hydromorphone median [25th, 75th] 4 [3, 5] and intrathecal morphine 3 [2, 4.5]) or at any time point (estimated difference, 0.5; 95% CI, 0 to 1; P = 0.139). Opioid received in the first 24 h did not differ between groups (median [25th, 75th] oral morphine milligram equivalents for intrathecal hydromorphone 30 [7.5, 45.06] vs. intrathecal morphine 22.5 [14.0, 37.5], P = 0.769). From Kaplan-Meier analysis, the median time to first opioid request was 5.4 h for hydromorphone and 12.1 h for morphine (log-rank test P = 0.200).
Conclusions: Although the hypothesis was that intrathecal morphine would provide superior analgesia to intrathecal hydromorphone, the results did not confirm this. At the doses studied, both intrathecal morphine and intrathecal hydromorphone provide effective postcesarean analgesia when combined with a multimodal analgesia regimen.
COA
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Publication ()
Figure 1. Introduction to morphine-related tolerance and dependence
