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The Journal of Sports Medicine and... Sep 1999Physical conditioning has been reported to increase liver oxidative metabolism determined by antipyrine clearance. The purpose of this investigation was to study effects...
BACKGROUND
Physical conditioning has been reported to increase liver oxidative metabolism determined by antipyrine clearance. The purpose of this investigation was to study effects of aerobic conditioning on the different metabolic pathways of antipyrine by comparing the production clearances of antipyrine metabolites.
PARTICIPANT
volunteers not engaged in the systematic practice of any sport (n = 14) were compared with aerobically-conditioned subjects (n = 14) (long distance runners, defined as men running > 80 km/week).
INTERVENTIONS
antipyrine was administered orally. Saliva samples were collected under basal conditions and at 8, 16, 24, 32 and 40 hrs following antipyrine administration. Urine was collected for 24 hrs after antipyrine ingestion.
MEASURES
endurance performance was expressed by the maximal oxygen uptake (VO2max), the ventilatory threshold and the 4 mM.l-1 lactate threshold (OBLA). Antipyrine pharmacokinetic parameters (antipyrine clearance and half-live) were obtained from saliva samples by the standard multiple-sample method.
RESULTS
VO2max, ventilatory threshold and OBLA were higher in trained than in control subjects (+32%, +16% and +74%, respectively). Salivary antipyrine clearance was higher, whether or not this variable was corrected for weight (+26% and +38%, respectively), and antipyrine half-life was significantly reduced (-31%) in runners. There was no significant change with training in the renal clearance of antipyrine or in the norantipyrine (NORA) formation clearance but significant increases were observed in hydroxymethylantipyrine (HMA) and 4-hydroxyantipyrine (OHA) formation clearances (+42 and +37%, respectively).
CONCLUSIONS
The findings indicate that aerobic conditioning leads to increased disposition of antipyrine and that the main metabolic pathways of the compound are changed differently.
Topics: Adult; Antipyrine; Exercise; Humans; Lactic Acid; Male; Metabolic Clearance Rate; Oxygen Consumption; Running; Saliva
PubMed: 10573660
DOI: No ID Found -
Alternative Therapies in Health and... Oct 2023Acute stroke is characterized by rapid progression, high mortality, and disability rates, making it a significant focus in clinical research. Brain-protective agents,... (Review)
Review
BACKGROUND
Acute stroke is characterized by rapid progression, high mortality, and disability rates, making it a significant focus in clinical research. Brain-protective agents, such as butylphthalide and edaravone, have emerged as important therapeutic options for acute stroke.
OBJECTIVE
This study aimed to explore how butylphthalide and edaravone promote healing in acute stroke, drawing on relevant data, literature, clinical experience, and personal concepts.
DESIGN
The study design involves a narrative review, which comprehensively explores the pathogenesis of stroke by referencing relevant data and literature. Clinical experience and personal insights were incorporated to provide a holistic understanding. The primary focus was analyzing the mechanisms through which butylphthalide and edaravone facilitate healing in stroke patients.
RESULTS
The review revealed that butylphthalide exhibited multiple beneficial effects, including the protection of mitochondria, reduction of the inflammatory response, enhancement of microcirculation, decrease in blood-brain barrier permeability, and improving nerve cell function. On the other hand, edaravone demonstrated its efficacy by reducing oxidative stress response, inhibiting inflammatory response, and regulating the metabolism of arachidonic acid and apoptosis. These findings highlight the distinct mechanisms through which butylphthalide and edaravone contribute to the healing process in patients with stroke.
CONCLUSIONS
This study highlights the positive impact of butylphthalide and edaravone on the therapeutic effect and short-term prognosis in acute stroke patients. The findings provide valuable guidance for future research and enhance our understanding of these drugs' mechanisms, offering the potential for improved stroke management and patient outcomes.
Topics: Humans; Edaravone; Sodium Chloride; Antipyrine; Stroke; Treatment Outcome
PubMed: 37499159
DOI: No ID Found -
Cancer Research Nov 1977The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake,...
The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake, and smoking and drinking history. The mean plasma clearance of antipyrine was 0.0475 +/- 0.009 liter/kg/hr in the tumor group and 0.0557 +/- 0.007 liter/kg/hr in the control group (p greater than 0.05). The antipyrine plasma elimination half-life was longer in the group with tumors (9.5 +/- 1.3 hr) compared to the control group (7.7 +/- 1.3 hr), but the difference was not statistically significant (p greater than 0.05). There was no difference between the groups in the excretion of two major antipyrine metabolites, 4-hydroxyantipyrine and N-demethylantipyrine, in a 48-hr urine sample. Thus, the presence of lung cancer in humans does not significantly alter antipyrine elimination.
Topics: Adult; Aged; Antipyrine; Female; Humans; Lung Neoplasms; Male; Metabolic Clearance Rate; Middle Aged
PubMed: 908027
DOI: No ID Found -
Drugs of Today (Barcelona, Spain : 1998) Jun 2018Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a fatal motor neuron degenerative disorder leading to paralysis and eventual death. At... (Review)
Review
Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a fatal motor neuron degenerative disorder leading to paralysis and eventual death. At present, we do not have any specific cure for this deadly disorder. Current drug therapy can only reduce morbidity in ALS patients. In 1995, riluzole was the first drug approved by the U.S. Food and Drug Administration (FDA) for ALS. After a long gap of 22 years, Mitsubishi Tanabe Pharma America got U.S. FDA approval for edaravone (Radicava) in May 2017 for the management of ALS. Edaravone, a novel neuroprotective agent, is indicated to slow down progression of ALS. In 2015, Mitsubishi Tanabe Pharma launched edaravone (Radicut) for the treatment of stroke and ALS in Japan. The U.S. FDA approved edaravone following clinical evidence from three clinical trials conducted in 368 ALS patients in Japan. Edaravone is awaiting approval by the European Medicines Agency (EMA) in Europe. Edaravone (60 mg) is administered by very slow intravenous infusion (60 minutes) in 28-day cycles. It has been shown to slow down the loss of physical function in ALS patients by 33% as compared to placebo. Edaravone is a strong antioxidant that prevents oxidative stress from inducing motor neuron death in ALS patients. Being a potent free radical scavenger, it has been shown to inhibit nitration of tyrosine residues in the cerebrospinal fluid and improve motor functions in mouse models of ALS. The product has been patented and the FDA has not approved any generic version of edaravone. This article discusses the preclinical pharmacology, pharmacokinetics, safety profile, clinical studies and drug interactions of edaravone (Radicava) in ALS.
Topics: Amyotrophic Lateral Sclerosis; Antipyrine; Edaravone; Free Radical Scavengers; Humans; Neuroprotective Agents
PubMed: 29998226
DOI: 10.1358/dot.2018.54.6.2828189 -
Amyotrophic Lateral Sclerosis &... Oct 2017The etiology of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress may be one of the major mechanisms involved. In vitro and in vivo data of edaravone... (Review)
Review
The etiology of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress may be one of the major mechanisms involved. In vitro and in vivo data of edaravone suggest that it may possess broad free radical scavenging activity and protect neurons, glia, and vascular endothelial cells against oxidative stress. During the 1980s and 1990s, edaravone was developed for the treatment of acute ischemic stroke. In 2001, a clinical program in ALS was initiated and five clinical studies were conducted in Japan. Phase III studies were designed to rapidly evaluate (within a 24-week double-blind study window) functional changes using the Revised ALS Functional Rating Scale (ALSFRS-R) as a primary endpoint. The study populations were selected according to these considerations and were further refined as the studies proceeded. Although the first phase III study did not meet its primary endpoint, post-hoc analyses showed an apparent effect of edaravone, when additional patient inclusion criteria defined by ALSFRS-R score, pulmonary function, certainty of ALS diagnosis, and duration of disease were applied. This population was hypothesized not only to have retained broad functionality and normal respiratory function at study baseline but also to be likely to show measurable disease progression over 24 weeks. A second confirmatory phase III study applying these refinements in patient selection was prospectively designed and successfully documented a statistically significant difference between the edaravone and placebo groups in the ALSFRS-R primary endpoint. This paper describes and reviews data pertinent to the potential mechanism of action of edaravone, and reviews the development history of edaravone for the treatment of ALS.
Topics: Amyotrophic Lateral Sclerosis; Antipyrine; Clinical Trials as Topic; Edaravone; Free Radical Scavengers; Humans; Oxidative Stress
PubMed: 28872907
DOI: 10.1080/21678421.2017.1353101 -
Current Opinion in Investigational... Nov 2000Mitsubishi-Tokyo (formerly Mitsubishi Chemical) is developing edaravone (norphenazone), a free radical scavenger, for the potential treatment of cardiovascular disease,... (Review)
Review
Mitsubishi-Tokyo (formerly Mitsubishi Chemical) is developing edaravone (norphenazone), a free radical scavenger, for the potential treatment of cardiovascular disease, cerebrovascular ischemia and cerebral edema. By February 2000, edaravone had been filed in Japan for the treatment of acute brain infarction, and was in phase III trials for subarachnoid hemorrhage [365460]. The compound blocks the action of the lipoperoxide, 15-HPETE, which normally increases with age and may be associated with neurodegeneration.
Topics: Antipyrine; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Drugs, Investigational; Edaravone; Free Radical Scavengers; Humans
PubMed: 11249718
DOI: No ID Found -
Toxicology and Applied Pharmacology May 1995The effects of repeated exposure to the pyrethroid insecticide flumethrin (40 mg/kg intraperitoneally once a day for 6 days) on the activity of cytochrome P450-dependent...
The effects of repeated exposure to the pyrethroid insecticide flumethrin (40 mg/kg intraperitoneally once a day for 6 days) on the activity of cytochrome P450-dependent monooxygenases and UDP-glucuronosyltransferase as well as on antipyrine disposition were investigated in male Wistar rats. Pretreatment with flumethrin decreased the activities of NADPH-cytochrome c reductase (38%), aniline hydroxylase (53%), aminopyrine N-demethylase (54%), and UDP-glucuronosyltransferase (34%), and the content of cytochrome P450 (36%) in hepatic microsomes. Total plasma clearance of antipyrine was decreased by flumethrin pretreatment (54%), while the elimination half-life at beta phase and the mean residence time of antipyrine were increased (96 and 88%, respectively). Urinary excretion of norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine was decreased by 60, 38, and 33%, respectively, in the 96 hr after flumethrin treatment. In addition, the rate constants for formation of each of these metabolites were decreased by an average of approximately 74%. These findings provide evidence that flumethrin exposure diminishes hepatic enzyme levels and catalytic activities of monooxygenase systems as well as oxidative metabolism of antipyrine.
Topics: Animals; Antipyrine; Cytochrome P-450 Enzyme System; Male; Microsomes, Liver; Pyrethrins; Rats; Rats, Wistar
PubMed: 7747277
DOI: 10.1006/taap.1995.1081 -
Mutation Research Nov 1988The drug antipyrine and its 4-substituted analogs, 4-aminoantipyrine, 4-dimethylaminoantipyrine (aminopyrine) and 4-nitrosoantipyrine were tested for mutagenicity...
The drug antipyrine and its 4-substituted analogs, 4-aminoantipyrine, 4-dimethylaminoantipyrine (aminopyrine) and 4-nitrosoantipyrine were tested for mutagenicity against the screening array of Salmonella typhimurium tester strains TA100, TA98, TA97, TA102 and TA104. Antipyrine and aminopyrine were nonmutagenic to all 5 tester strains even in the presence of S9. 4-Aminoantipyrine was directly mutagenic to TA97 only and the presence of S9 slightly increased its activity. 4-Nitrosoantipyrine was directly mutagenic to all tester strains used and S9 decreased its activity except with strain TA102. The possible long-term hazards of C-nitroso compounds derived from drugs and dietary constituents are discussed in view of their pluripotent direct genotoxicity.
Topics: Aminopyrine; Ampyrone; Animals; Antipyrine; Biotransformation; Mass Spectrometry; Microsomes, Liver; Mutagenicity Tests; Mutation; Rats; Salmonella typhimurium
PubMed: 3059178
DOI: 10.1016/0165-1218(88)90117-6 -
Xenobiotica; the Fate of Foreign... Apr 1983The influence of pretreatment of rats with 9-hydroxyellipticine and 3-methylcholanthrene on different enzymes of the hepatic mixed-function oxidase system were studied...
The influence of pretreatment of rats with 9-hydroxyellipticine and 3-methylcholanthrene on different enzymes of the hepatic mixed-function oxidase system were studied using antipyrine as model compound. Antipyrine half-lives and clearances were estimated in blood, and the metabolite profile was determined in urine. 3-Methylcholanthrene treatment resulted in an increase in antipyrine clearance from 17 to 75 ml/min per kg. Partial clearance of formation of 4-hydroxyantipyrine was selectively increased from 3.9 to 28.2 ml/min kg, whereas clearance of 3-hydroxymethylantipyrine was decreased from 3.2 to 1.2 ml/min per kg. Norantipyrine formation was increased from 2.7 to 7.2 ml/min per kg, while 4,4'-dihydroxyantipyrine formation was unchanged. 9-Hydroxyellipticine treatment resulted in no change in the total clearance, and only the clearance of 4,4'-dihydroxyantipyrine was decreased, from 2.5 to 1.5 ml/min per kg. After pretreatment with 3-methylcholanthrene, 9-hydroxyellipticine treatment resulted in a selective decrease in the clearances of 4-hydroxyantipyrine, from 28.2 to 15.8 ml/min per kg, and of 4,4'-hydroxyantipyrine, from 3.8 to 1.6 ml/min per kg. From these results it is concluded, that 9-hydroxyellipticine is a selective inhibitor of the activity of some of the cytochrome P-450s involved in antipyrine metabolism, though this inhibition does not effect all of these enzymes, nor is it restricted to polycyclic hydrocarbon-induced activity. These results further substantiate the value of antipyrine as a model substrate, for they indicate that the formation of all four metabolites of antipyrine in rats is mediated by different (iso-)enzymes.
Topics: Alkaloids; Animals; Antipyrine; Edaravone; Ellipticines; Kinetics; Methylcholanthrene; Rats; Rats, Inbred Strains
PubMed: 6624137
DOI: 10.3109/00498258309052258 -
Spectrochimica Acta. Part A, Molecular... Sep 2013Organic compounds are attracting greater attention largely in the recent years owing to their potential applications in the functional materials. Herein we reported the...
Organic compounds are attracting greater attention largely in the recent years owing to their potential applications in the functional materials. Herein we reported the structural and photophysical properties of 4-(3-fluorobenzylideneamino)antipyrine. The studied molecule adopts a trans configuration about the imine bond, and forms a non-planar molecular device consisted of two effectively conjugated π-electron moieties. The stronger vibrational and nonlinear optical activities are tightly related to the molecular structural characteristics revealed by the analysis on vibrational modes and frontier molecular orbitals. The intramolecular electrons can be separated by the electron-transporting with specified photon-absorbing theoretically. The total molecular dipole moment, mean linear polarizability and first-order hyperpolarizability calculated at B3LYP/6-31G(d) level are 1.5390 Debye, 35.6075 Å(3) and 1.5391×10(-29) cm(5)/esu, respectively. The reported results indicate that the compound is a promising candidate of photoresponsive materials.
Topics: Antipyrine; Crystallography, X-Ray; Hydrogen Bonding; Light; Models, Molecular; Molecular Conformation; Nonlinear Dynamics; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Vibration
PubMed: 23711396
DOI: 10.1016/j.saa.2013.04.099