naloxone brands

Molecular formula: C19H21NO4

Naloxone is a competitive inhibitor of the µ-opioid receptor. Naloxone antagonizes the action of opioids, reversing their effects. If a patient has not taken opioids, naloxone does not have a significant effect on patients. Naloxone hydrochloride is essentially a pure opiate antagonist. The precise mechanism of action of the opiate antagonist effects of naloxone is not fully understood. Naloxone is thought to act as a competitive antagonist at mu, kappa, and sigma opiate receptors in the CNS; it is thought that the drug has the highest affinity for the mu receptor. In contrast to levallorphan or nalorphine, naloxone has little or no agonistic activity. When administered in usual doses to patients who have not recently received opiates, naloxone exerts little or no pharmacologic effect. Even extremely high doses of the drug (10 times the usual therapeutic dose) produce insignificant analgesia, only slight drowsiness, and no respiratory depression, psychotomimetic effects, circulatory changes, or miosis. In patients who have received large doses of morphine or other analgesic drugs with morphine-like effects, naloxone antagonizes most of the effects of the opiate. There is an increase in respiratory rate and minute volume, arterial PCO2 decreases toward normal, and blood pressure returns to normal if depressed. Unlike nalorphine or levallorphan, naloxone antagonizes mild respiratory depression caused by small doses of opiates. Because the duration of action of naloxone is generally shorter than that of the opiate, the effects of the opiate may return as the effects of naloxone dissipate. Naloxone antagonizes opiate-induced sedation or sleep. Reports are conflicting on whether or not the drug modifies opiate-induced excitement or seizures. Heat shock protein (HSP)60 is primarily a mitochondrial protein. Previous experiments have found that changes in the location of intracellular HSP60 have been associated with apoptosis. Extracellular HSP60 mediates apoptosis via its ligand, Toll-like receptor (TLR)-4. TLR-4 is an important factor expressed on microglia, with a central role in generating neuroimmune responses in the pathogenesis of neurodegenerative disorders. Naloxone is a highly effective nonselective opioid receptor antagonist, and has been reported to be pharmacologically beneficial for the treatment of brain diseases through inhibiting microglia activation. However, the mechanisms underlying these beneficial effects of naloxone remain poorly understood. The present study aimed to investigate the role of HSP60 in the neuroprotective effects of naloxone on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells and the possible signaling pathways involved. The results demonstrated that naloxone significantly inhibited the expression and release of HSP60 in BV2 cells. The expression levels of heat shock factor (HSF)-1 were upregulated in LPS-activated BV2 cells, which indicated that the increased expression of HSP60 was driven by HSF-1 activation. However, increased HSF-1 levels may be downregulated by naloxone. The levels of TLR-4 were elevated in activated BV2 cells, and then inhibited by naloxone. Activation of TLR-4 is characterized by activation of nuclear factor-kB (NF-kB) followed by the production of various proinflammatory and neurotoxic factors. Data from the present study demonstrated that naloxone reduced the expression levels of NF-kB and its upstream protein caspase-3, and reduced the LPS-induced production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor a, interleukin-1beta and interleukin-6 in BV2 microglia. In light of this data, it was concluded that naloxone may exert its neuroprotective and anti-inflammatory effects by inhibiting microglia activation through a HSP60-TLR-4-NF-kB signaling pathway. Phosphoinositide 3-kinase (PI3K) delta and gamma (the p110delta and p110gamma isoforms of PI3K) actively participate in the process of

Source: PubChem (NCBI) · compound 5284596