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Brain Research Bulletin Jul 2024Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and... (Review)
Review
Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.
Topics: Hyperuricemia; Allopurinol; Humans; Epilepsy; Animals; Oxidative Stress; Uric Acid; Xanthine Oxidase; Brain
PubMed: 38723694
DOI: 10.1016/j.brainresbull.2024.110973 -
American Journal of Ophthalmology Sep 1984We conducted a two-part study to determine whether any positive association between the use of allopurinol and the development of cataracts could be demonstrated. Study...
We conducted a two-part study to determine whether any positive association between the use of allopurinol and the development of cataracts could be demonstrated. Study 1 included 251 Boston-area patients hospitalized for cataract and 753 matched controls. Two cataract patients were regular allopurinol users as compared with six control patients. The relative risk for cataract comparing allopurinol users with nonusers was 1.0 (95% exact confidence interval 0.14, 4.7). Study 2 included 389 patients from the Puget Sound, Washington, area who were hospitalized for cataract surgery during a five-year period (551,543 person-years). The rate of hospitalization for cataract in patients 30 to 49 years old was 0/992 person-years for allopurinol users and 78/366,960 (2.1 per 10(4)) person-years for nonusers. The rate of hospitalization for cataract in patients 50 to 64 years old was 3/2,270 (13.2 per 10(4)) person-years for allopurinol users and 308/184,583 (16.7 per 10(4)) person-years for nonusers.
Topics: Allopurinol; Cataract; Humans
PubMed: 6476060
DOI: 10.1016/0002-9394(84)90328-3 -
Clinical Pharmacokinetics 2007Allopurinol is the drug most widely used to lower the blood concentrations of urate and, therefore, to decrease the number of repeated attacks of gout. Allopurinol is... (Review)
Review
Allopurinol is the drug most widely used to lower the blood concentrations of urate and, therefore, to decrease the number of repeated attacks of gout. Allopurinol is rapidly and extensively metabolised to oxypurinol (oxipurinol), and the hypouricaemic efficacy of allopurinol is due very largely to this metabolite. The pharmacokinetic parameters of allopurinol after oral dosage include oral bioavailability of 79 +/- 20% (mean +/- SD), an elimination half-life (t((1/2))) of 1.2 +/- 0.3 hours, apparent oral clearance (CL/F) of 15.8 +/- 5.2 mL/min/kg and an apparent volume of distribution after oral administration (V(d)/F) of 1.31 +/- 0.41 L/kg. Assuming that 90 mg of oxypurinol is formed from every 100mg of allopurinol, the pharmacokinetic parameters of oxypurinol in subjects with normal renal function are a t((1/2)) of 23.3 +/- 6.0 hours, CL/F of 0.31 +/- 0.07 mL/min/kg, V(d)/F of 0.59 +/- 0.16 L/kg, and renal clearance (CL(R)) relative to creatinine clearance of 0.19 +/- 0.06. Oxypurinol is cleared almost entirely by urinary excretion and, for many years, it has been recommended that the dosage of allopurinol should be reduced in renal impairment. A reduced initial target dosage in renal impairment is still reasonable, but recent data on the toxicity of allopurinol indicate that the dosage may be increased above the present guidelines if the reduction in plasma urate concentrations is inadequate. Measurement of plasma concentrations of oxypurinol in selected patients, particularly those with renal impairment, may help to decrease the risk of toxicity and improve the hypouricaemic response. Monitoring of plasma concentrations of oxypurinol should also help to identify patients with poor adherence. Uricosuric drugs, such as probenecid, have potentially opposing effects on the hypouricaemic efficacy of allopurinol. Their uricosuric effect lowers the plasma concentrations of urate; however, they increase the CL(R) of oxypurinol, thus potentially decreasing the influence of allopurinol. The net effect is an increased degree of hypouricaemia, but the interaction is probably limited to patients with normal renal function or only moderate impairment.
Topics: Allopurinol; Humans; Metabolic Networks and Pathways; Models, Theoretical; Oxypurinol; Pharmacokinetics
PubMed: 17655371
DOI: 10.2165/00003088-200746080-00001 -
Lancet (London, England) Oct 1976
Topics: Allopurinol; Arteritis; Female; Giant Cell Arteritis; Gout; Humans; Middle Aged
PubMed: 62137
DOI: 10.1016/s0140-6736(76)90567-5 -
British Medical Journal Apr 1979
Topics: Adult; Allopurinol; Drug Hypersensitivity; Gout; Humans; Male
PubMed: 435956
DOI: 10.1136/bmj.1.6169.988 -
Nature Reviews. Rheumatology Oct 2023Xanthine oxidase inhibitors such as allopurinol and febuxostat have been the mainstay urate-lowering therapy (ULT) for treating hyperuricaemia in patients with gout.... (Review)
Review
Xanthine oxidase inhibitors such as allopurinol and febuxostat have been the mainstay urate-lowering therapy (ULT) for treating hyperuricaemia in patients with gout. However, not all patients receiving oral ULT achieve the target serum urate level, in part because some patients cannot tolerate, or have actual or misconceived contraindications to, their use, mainly due to comorbidities. ULT dosage is also limited by formularies and clinical inertia. This failure to sufficiently lower serum urate levels can lead to difficult-to-treat or uncontrolled gout, usually due to poorly managed and/or under-treated gout. In species other than humans, uricase (urate oxidase) converts urate to allantoin, which is more soluble in urine than uric acid. Exogenic uricases are an exciting therapeutic option for patients with gout. They can be viewed as enzyme replacement therapy. Uricases are being used to treat uncontrolled gout, and can achieve rapid reduction of hyperuricaemia, dramatic resolution of tophi, decreased chronic joint pain and improved quality of life. Availability, cost and uricase immunogenicity have limited their use. Uricases could become a leading choice in severe and difficult-to-treat gout as induction and/or debulking therapy (that is, for lowering of the urate pool) to be followed by chronic oral ULT. This Review summarizes the evidence regarding available uricases and those in the pipeline, their debulking effect and their outcomes related to gout and beyond.
Topics: Humans; Gout Suppressants; Uric Acid; Hyperuricemia; Urate Oxidase; Quality of Life; Gout; Allopurinol
PubMed: 37684360
DOI: 10.1038/s41584-023-01006-3 -
Journal of Hypertension Dec 2019Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high-dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well-controlled blood pressure but without established cardiovascular disease.
METHODS
We conducted a mechanistic proof-of-concept randomized, placebo-controlled, double-blind trial of allopurinol (600 mg/day) versus placebo on LV mass regression. Duration of treatment was 12 months. LV mass regression was assessed by Cardiac Magnetic Resonance. Secondary outcomes were changes in endothelial function (flow-mediated dilatation), arterial stiffness (pulse wave velocity) and biomarkers of oxidative stress.
RESULTS
Seventy-two patients were randomized into the trial. Mean baseline urate was 362.2 ± 96.7 μmol/l. Despite good blood pressure control, LV mass regression was significantly reduced in the allopurinol cohort compared with placebo (LV mass -0.37 ± 6.08 versus -3.75 ± 3.89 g; P = 0.012). Oxidative stress markers (thiobarbituric acid reactive substances) were significantly higher in the allopurinol group versus placebo (0.26 ± 0.85 versus -0.34 ± 0.83 μmol/l; P = 0.007). Other markers of vascular function were not significantly different between the two groups.
CONCLUSION
Treatment with high-dose allopurinol in normouricemic controlled hypertensive patients and LV hypertrophy is detrimental. It results in reduced LV mass regression and increased oxidative stress over a 12-month period. This may be because of an adverse impact on redox balance. Cohort selection for future cardiovascular trials with allopurinol is crucial.
Topics: Allopurinol; Blood Pressure; Double-Blind Method; Essential Hypertension; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Oxidative Stress; Pulse Wave Analysis
PubMed: 31268872
DOI: 10.1097/HJH.0000000000002189 -
Journal of Biological Inorganic... Jun 2021Metal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer...
Metal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer potential of ruthenium(II)/allopurinol complexes called [RuCl(allo)(PPh)] (1) and [RuCl(allo)(dppb)] (2), where allo means allopurinol, PPh is triphenylphosphine and dppb, 1,4-bis(diphenylphosphino)butane. The complexes were synthesized and characterized by elemental analysis, IR, UV-Vis and NMR spectroscopies, cyclic voltammetry, molar conductance measurements, as well as the X-ray crystallographic analysis of complex 2. The antitumor effects of compounds were determined by cytotoxic activity and cellular and molecular responses to cell death mechanisms. Complex 2 showed good antitumor profile prospects because in addition to its cytotoxicity, it causes cell cycle arrest, induction of DNA damage, morphological and biochemical alterations in the cells. Moreover, complex 2 induces cell death by p53-mediated apoptosis, caspase activation, increased Beclin-1 levels and decreased ROS levels. Therefore, complex 2 can be considered a suitable compound in antitumor treatment due to its cytotoxic mechanism.
Topics: Allopurinol; Animals; Antineoplastic Agents; Ascitic Fluid; Cell Cycle; Cell Migration Assays; Cell Survival; Cells, Cultured; Female; Fibroblasts; Humans; Mammary Neoplasms, Animal; Mice; Neoplasms, Experimental; Ruthenium Compounds
PubMed: 33837856
DOI: 10.1007/s00775-021-01862-y -
Deutsche Medizinische Wochenschrift... Sep 1977
Topics: Allopurinol; Erectile Dysfunction; Female; Humans; Male; Sexual Dysfunction, Physiological
PubMed: 561685
DOI: No ID Found -
Annals of the Rheumatic Diseases Jun 1987
Topics: Allopurinol; Gout; Humans; Oxypurinol; Pyrimidines; Uricosuric Agents
PubMed: 3632073
DOI: 10.1136/ard.46.6.493-a