European journal of pharmacology
-
7-Hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) is a novel coumarin derivative synthesized in our laboratory. The purpose of the current study was to determine the neuroprotective effects of IMM-H004 on PC12 cells and its potential mechanism of action. PC12 cells were subject to oxygen and glucose deprivation (OGD) followed by the restoration of oxygen and glucose (R), which mimics ischemia and reperfusion in vivo. ⋯ These changes were significantly inhibited by IMM-H004. IMM-H004 also significantly inhibited OH formation, determined by electron spin resonance, which indicates that it is a potent free-radical scavenger. This study has demonstrated that IMM-H004 protects PC12 cells against OGD/R-induced apoptosis, at least in part, by scavenging excessive ROS and inhibiting the mitochondrion-dependent apoptotic pathway.
-
Crytotanshinone (CTN), one of the main constituents of tanshinones, has been reported to exhibit anti-tumor, anti-inflammatory and other important therapeutic activities. The aim of this study was to investigate the potential therapeutic effects of CTN on murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Male BALB/c mice were pretreated with dexamethasone or CTN 1h before intranasal instillation of LPS. ⋯ Additionally, western blotting showed that CTN efficiently inhibited the phosphorylation of IκB-α, p65 NF-κB and the expression of TLR4. Taken together, our results suggest that the anti-inflammatory effects of CTN against LPS-induced acute lung injury may be due to its ability to inhibit TLR4 mediated NF-κB signaling pathways. CTN may be a promising potential therapeutic reagent for ALI treatment.
-
Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. ⋯ Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.
-
Clinical research shows that postoperative nausea and vomiting (PONV) is caused primarily by the use of inhalational anesthesia and opioid analgesics. PONV is also increased by several risk predictors, including a young age, female sex, lack of smoking, and a history of motion sickness. Genetic studies are beginning to shed light on the variability in patient experiences of PONV by assessing polymorphisms of gene targets known to play roles in emesis (serotonin type 3, 5-HT3; opioid; muscarinic; and dopamine type 2, D2, receptors) and the metabolism of antiemetic drugs (e.g., ondansetron). ⋯ This gap in knowledge has limited the development of novel effective therapies of PONV. The current review presents the state of knowledge on the biological mechanisms responsible for PONV, summarizing both preclinical and clinical evidence. Finally, potential ways to advance the research of PONV and more recent developments on the study of postdischarge nausea and vomiting (PDNV) are discussed.
-
Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the palliative care population. Unfortunately, among the adverse effects of opioids that may be experienced along with analgesia is nausea, vomiting, and/or retching. Although it is conceivable that in the future, using combination agents (opioids combined with agents which may nullify emetic effects), currently nausea/vomiting remains a significant issue for certain patients. However, there exists potential current strategies that may be useful in efforts to diminish the frequency and/or intensity of opioid-induced nausea/vomiting (OINV).