title: Nitrogen, oxygen or sulfur containing heterocyclic compounds as analgesic drugs used as modulators of the nitroxidative stress.
abstract: Numerous lines of evidence suggest that heterocyclic compounds used as analgesic, anti-inflammatory and anti-migraine agents can be potent regulators of the nitroxidative stress and targeting free nitrogen and oxygen radicals is a very promising strategy for future pain management. Both classical analgesics (nonsteroidal anti-inflammatory drugs, opioid drugs) and many analgesic adjuvants, including desipramine, duloxetine, fluoxetine, paroxetine, escitalopram, phenytoin or carbamazepine and α-lipoic acid can modulate the balance between pro-oxidant and antioxidant processes in the mammalian tissues and these properties of drugs such as indomethacin, meloxicam, tenoxicam, valdecoxib or some metabolites of analgesic drugs formed by the activity of tissue peroxidases may contribute to their clinical efficacy and drug-related toxic effects, including gastrointestinal ulcers, hepatic failure, agranulocytosis, aplastic anemia, neutropenia, opiate-induced hyperalgesia and tolerance. The antioxidant capacities of novel heterocyclic compounds, including the compounds acting either by prevention of formation or catalyzed decomposition of peroxynitrite anion (ONOO-), namely the peroxynitrite decomposition catalysts or as superoxide (O2 •-)-scavengers which are the functional mimetics of superoxide dismutase (SOD) enzymes (SODm), as well as the derivatives of 6-nitro-3,4-methylenedioxyphenyl-Nacylhydrazone (LASSBio-881) or γ-butyrolactone (LPP1, BM113, BM113A, BM138 and BM138A) are also discussed as potent and promising future heterocyclic analgesics.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland. salat.kinga@gmail.com
authors.forename: Kinga
authors.initials: K
authors.lastname: Salat
authors.forename: Andrzej
authors.initials: A
authors.lastname: Moniczewski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Librowski
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009584:Nitrogen / Q000032:analysis*; D015538:Nitrosation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000032:analysis*; D013455:Sulfur / Q000032:analysis*
chemical_list: D000700:Analgesics; D006571:Heterocyclic Compounds; D013455:Sulfur; D009584:Nitrogen; D010100:Oxygen