Disease relevance of KBioSS_002161

• The mutant gene responsible for obesity in the ob/ob mouse was recently identified by positional cloning (Zhang Y., R. Proenca, M. Maffel, M. Barone, L. Leopold, and J.M. Friedman. 1994. Nature (Lond.) 372:425) [1].
• Genetic factors and risk of agranulocytosis from metamizol [2].
• TNF evoked a time- and dose-dependent muscle hyperalgesia within several hours after injection that was totally reversed by systemic treatment with the non-opioid analgesic metamizol [3].
• Using metamizole as an easily nitrosatable precursor, two strains, Campylobacter jejuni and Helicobacter pylori, were shown to catalyse nitrosation in the presence of nitrite at pH 7 [4].
• The aim of this study is to compare intravenous metamizol with placebo in the acute treatment of migraine with aura, migraine without aura and episodic tension-type headache [5].

Psychiatry related information on KBioSS_002161

• Analgin and aspirin increased the pain threshold relatively at a low dose [6].
• In patients with a history of drug abuse, metamizol is in fact the drug of choice for immediate postoperative analgesic treatment [7].

High impact information on KBioSS_002161

• P-selectin glycoprotein ligand-1 (PSGL-1) is the high affinity counter-receptor for P-selectin on myeloid cells (Sako, D., Chang, X.J., Barone, K.M., Vachino, G., White, H.M., Shaw, G., Veldman, G.M., Bean, K.M., Ahern, T.J., Furie, B., Cumming, D. A., and Larsen, G. R. (1993) Cell 75, 1179-1186) [8].
• Dipyrone (metamizole) metabolites interfere with HPLC analysis of plasma catecholamines but not with the determination of urinary catecholamines [9].
• The NSAID dipyrone (metamizol) has been shown to engage opioidergic circuits at the PAG, the NRM and the spinal cord, but it is unknown whether this can be generalized to typical NSAIDs and to systemic administration [10].
• In the first part of this study, we analyzed the effectiveness of buprenorphine, tramadol, ketorolac and metamizol in the clinical setting, where the placebo effect was completely eliminated by means of hidden infusions [11].
• The opioid receptor antagonist naloxone completely blocked morphine induction of GPDH but had no effect on GPDH induction by noxious heat stimulation or metamizol treatment, implicating different mechanisms of GPDH induction [12].

Chemical compound and disease context of KBioSS_002161

• Efficacy and safety of metamizol vs. acetylsalicylic acid in patients with moderate episodic tension-type headache: a randomized, double-blind, placebo- and active-controlled, multicentre study [13].
• STUDY DESIGN AND METHODS: This report describes the results of serologic testing and treatment in two children with immune neutropenia related to cefotaxime and metamizole, respectively [14].
• Noramidopyrine (Metamizol) and acute interstitial nephritis [15].
• Metabolic effects of i.v. propacetamol, metamizol or external cooling in critically ill febrile sedated patients [16].
• Comparison of cizolirtine citrate and metamizol sodium in the treatment of adult acute renal colic: a randomized, double-blind, clinical pilot study [17].

Biological context of KBioSS_002161

• In the patients exposed to metamizol, an A24-B7 haplotype was found with a frequency higher than that in the non-exposed patients and the reference group (p < 0.05) [2].
• Only at concentrations above 100 microM, well over the pharmacological range, metamizol-induced apoptosis in about 30% of the HL60 promyelocytes, while HL60-granulocytic terminally differentiated cells were more resistant to this apoptotic action [18].
• When the effects of metamizol were compared with those of acetylsalicylic acid (ASA) and diclofenac on cell viability, at equivalent concentrations used in analgesic and antipyretic therapy (75 microM for metamizol, and ASA and 3 microM for diclofenac) their apoptotic effects were similar [18].
• The IC50 values of metamizol for cyclooxygenase-1 in intact bovine aortic endothelial cells (BAEC) cells and human platelets were 1730 +/- 150 microg/ml and 486 +/- 56 microg/ml, respectively [19].
• For a 1 degrees C temperature decrease, the energy expenditure index increased by 5% with external cooling and decreased by 7% and 8% in the metamizol and propacetamol groups, respectively [20].

Anatomical context of KBioSS_002161

• Activity in ascending axons responding to afferent C fibre stimulation was mostly depressed by i.t. injection of metamizol (40, 80 and 140 mg/kg) in rats with an intact spinal cord [21].
• Metamizol (140 mg/kg) i.v. increased the activity of neurones in the PAG and reduced that of neurones in the substantia nigra [21].
• Isolated buffy coat leukocytes were stimulated in vitro with aspirin, paracetamol, metamizol, diclofenac, and naproxen [22].
• These and other results suggest that metamizol activates endogenous opioid systems and that nonopioid analgesics may, by an action upon the central nervous system, lead to opioid tolerance and the risk of opioid withdrawal [23].
• Microinjection of metamizol (dipyrone), a widely used nonopioid analgesic, into the periaqueductal grey matter (PAG) of rats activates pain-modulating systems in the nucleus raphe magnus and inhibits spinal nociceptive neurons and the tail-flick reflex [23].

Associations of KBioSS_002161 with other chemical compounds

• These results demonstrate that metamizol, MAA, ASA, and diclofenac, at pharmacological concentrations, neither affect the granulocytic differentiation process nor induce relevant apoptosis on terminally differentiated granulocytes [18].
• BACKGROUND: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in drug-metabolizing genes [24].
• Use of intravenous patient-controlled analgesia for the documentation of synergy between tramadol and metamizol [25].
• METHODS: Skin-tests (prick and intradermal) were performed with metamizole, metronidazole, and espyramicine [26].
• Physical examination findings and mean VAS pain intensity scores at baseline (mean [SD], 79.42 [7.89] mm and 82.59 [10.50] mm in the cizolirtine and metamizol groups, respectively) were similar in both groups [17].

Gene context of KBioSS_002161

• CONCLUSIONS: In addition to inhibition of PG synthesis, damage induced by metamizol was associated with an inhibition of the NO/cGMP pathway and cNOS activity [27].
• Metamizol inhibited purified cyclooxygenase-1 and cyclooxygenase-2 with an IC50 of about 150 microg/ml [19].
• Noraminophenazone prevented the urocortin-induced increase in colon temperature and attenuated the already existing elevated body temperature [28].
• Use of CD63 expression as a marker of in vitro basophil activation and leukotriene determination in metamizol allergic patients [29].
• In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid [30].

Analytical, diagnostic and therapeutic context of KBioSS_002161

• Metamizol administered by microinjection into the PAG prolonged the tail-flick latency (15-100 micrograms) and depressed C fibre-evoked activity in ascending axons (100 micrograms) [21].
• The HL-A2 antigen was absent in four of the five metamizol-associated agranulocytosis cases (20%), while in the control group it was present in 56% [2].
• An intramuscular injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the PACAP-38-induced hyperthermia [31].
• While the analgesic effect of morphine (2 mg/kg) was antagonized by naloxone (1 mg/kg), the opioid antagonist did not reverse the analgesia induced by the combination of metamizol and morphine [32].
• Skin tests with metamizol, FAST, and CAST were performed [29].

References