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Biochemical Pharmacology Feb 2014Vidarabine was the first clinically approved antiviral drug, but due to safety and efficacy issues the drug is currently only used topically for herpes virus keratitis.... (Review)
Review
Vidarabine was the first clinically approved antiviral drug, but due to safety and efficacy issues the drug is currently only used topically for herpes virus keratitis. Scientific interest in vidarabine has been recently renewed due to the fact that the compound exhibits beneficial effects in animal models of heart failure and cancer, replicating effects of the knockout of adenylyl cyclase 5 (AC5). Therefore, vidarabine has been suggested to mediate these effects via selective inhibition of AC5. Based on these results, clinical studies with vidarabine in humans for heart failure and cancer have been proposed. Here, evidence is presented that vidarabine is neither a potent nor a selective AC5 inhibitor. Greatest caution should be exerted when proposing new mechanisms of actions and clinical uses for vidarabine.
Topics: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Animals; Antiviral Agents; Heart Failure; Humans; Isoenzymes; Neoplasms; Vidarabine
PubMed: 24398424
DOI: 10.1016/j.bcp.2013.12.025 -
Journal of Neurology, Neurosurgery, and... Dec 1984Vidarabine (adenine arabinoside, ara-a) has been found to be useful in the treatment of various viral infections. Its adverse neurological effects include tremor and...
Vidarabine (adenine arabinoside, ara-a) has been found to be useful in the treatment of various viral infections. Its adverse neurological effects include tremor and encephalopathy. Two cases of vidarabine encephalopathy are reported and the five other cases in the literature are reviewed. The clinical features of the tremor and encephalopathy are discussed.
Topics: Adult; Electroencephalography; Evoked Potentials; Female; Herpes Zoster; Humans; Male; Middle Aged; Substance-Related Disorders; Tremor; Vidarabine
PubMed: 6512557
DOI: 10.1136/jnnp.47.12.1351 -
Drugs Oct 1980Vidarabine is the first drug to become generally available in the USA for parenteral treatment of life-threatening or debilitating herpes simplex virus infections of... (Review)
Review
Vidarabine is the first drug to become generally available in the USA for parenteral treatment of life-threatening or debilitating herpes simplex virus infections of man. For the past decade laboratory and clinical studies have been in progress to assess the pharmacology of the compound, its mechanism of action and its potential usefulness in clinical investigations. Currently, clinical usefulness has been established for herpes simplex infections of the eye and brain. Further studies in progress are evaluating the drug's ability to prevent progressive disease from herpes zoster in the immunocompromised patient, reduce mortality and morbidity from neonatal herpes simplex virus infection and improve outcome of chronic hepatitis B infection.
Topics: Antiviral Agents; Eye Diseases; Humans; Kinetics; Vidarabine; Virus Diseases; Wound Healing
PubMed: 6998693
DOI: 10.2165/00003495-198020040-00002 -
Antimicrobial Agents and Chemotherapy May 1986A 24-year-old man with disseminated herpes zoster, which occurred 9 months after bone marrow transplantation for chronic myeloid leukemia, developed encephalopathy and...
A 24-year-old man with disseminated herpes zoster, which occurred 9 months after bone marrow transplantation for chronic myeloid leukemia, developed encephalopathy and immobilizing myoclonus after 7 days of vidarabine treatment (10 mg/kg of body weight per day). Only mild hepatic dysfunction was a risk factor for a toxic reaction. After the vidarabine therapy was stopped, the symptoms worsened until treatment with hydration, large doses of chlordiazepoxide, and protective care gave symptomatic relief.
Topics: Adult; Brain Diseases; Herpes Zoster; Humans; Male; Myoclonus; Vidarabine
PubMed: 3729352
DOI: 10.1128/AAC.29.5.933 -
JAMA Jan 1979
Topics: Brain; Hepatitis B; Humans; Kidney; Liver; Vidarabine
PubMed: 758490
DOI: 10.1001/jama.1979.03290270020010 -
The Medical Letter on Drugs and... May 1977
Clinical Trial
Topics: Clinical Trials as Topic; Humans; Keratitis, Dendritic; Vidarabine
PubMed: 323676
DOI: No ID Found -
Drug and Therapeutics Bulletin May 1979
Topics: Humans; Keratitis, Dendritic; Ointments; Vidarabine
PubMed: 467237
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Letters Nov 2021Vidarabine (ARA) was one of the earliest marine-related compounds to be used clinically for antiviral therapy, however, its fast metabolism is the main defect of this...
Vidarabine (ARA) was one of the earliest marine-related compounds to be used clinically for antiviral therapy, however, its fast metabolism is the main defect of this drug. To overcome this, we designed and synthesized a group of phosphamide-modified ARA compounds using ProTide technology. With a phosphamide modification, these compounds could become the substrate of specific phospholipase enzymes expressed in the liver. Among all 16 synthesized compounds, most showed stronger activity against herpes simplex virus type 1 (HSV-1) than ARA (EC of approximately 10 μM). The top three compounds were compound 2 (EC = 0.52 ± 0.04 μM), compound 6 (EC = 1.05 ± 0.09 μM) and compound 15 (EC = 1.18 ± 0.08 μM) (about 2 times higher than Sp type compound 2). This study provides evidence for use of the phosphamide modification, which could give ARA higher activity and liver cell targeting.
Topics: Antiviral Agents; Dimethoate; Dose-Response Relationship, Drug; Herpes Simplex; Herpesvirus 1, Human; Humans; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Vidarabine
PubMed: 34624489
DOI: 10.1016/j.bmcl.2021.128405 -
The Journal of Toxicological Sciences Feb 2016Vidarabine has been used for the treatment of patients with local and systemic herpes virus infection; moreover, it was recently reported that it inhibits cardiac type 5...
Antiviral drug vidarabine possessing cardiac type 5 adenylyl cyclase inhibitory property did not affect cardiohemodynamic or electrophysiological variables in the halothane-anesthetized dogs.
Vidarabine has been used for the treatment of patients with local and systemic herpes virus infection; moreover, it was recently reported that it inhibits cardiac type 5 adenylyl cyclase. Furthermore, vidarabine has been shown to suppress atrial fibrillation and improve congestive heart failure in experimental models of mice induced by the isoproterenol infusion. Since information that can explain its experimentally demonstrated efficacy against congestive heart failure and atrial fibrillation remains limited, in this study we precisely assessed cardio-electropharmacological effect using the halothane-anesthetized canine model. Vidarabine was intravenously administrated in three escalating doses of 1, 10, 100 mg/kg over 10 min with a pause between the doses (n = 4). Meanwhile, the vehicle dimethyl sulfoxide in volumes of 0.033, 0.033 and 0.33 mL/kg was intravenously administrated in the same manner as was vidarabine (n = 4). No significant difference was detected in any cardiohemodynamic or electrophysiological variables between the vehicle- and vidarabine-treated groups, which indicates that effective doses of vidarabine adequately inhibiting type 5 adenylyl cyclase did not affect the cardiovascular variables in vivo at all, showing its cardiac safety profile under physiological condition. Thus, the clinical utility of vidarabine might be limited to the pathological situation including congestive heart failure with increased adrenergic tone and/or sympathetic nerve-dependent atrial fibrillation.
Topics: Adenylyl Cyclase Inhibitors; Anesthesia, Inhalation; Animals; Antiviral Agents; Atrial Fibrillation; Dogs; Electrophysiological Phenomena; Halothane; Heart Failure; Hemodynamics; Infusions, Intravenous; Male; Models, Animal; Vidarabine
PubMed: 26763398
DOI: 10.2131/jts.41.115 -
Fundamental & Clinical Pharmacology 1992The pharmacokinetics of vidarabine were studied in 8 patients with polyarteritis nodosa related to hepatitis B virus infection. The drug was administered by continuous...
The pharmacokinetics of vidarabine were studied in 8 patients with polyarteritis nodosa related to hepatitis B virus infection. The drug was administered by continuous infusion for three weeks at doses of 15 (1 week) and 7.5 (2 weeks) mg/kg per day, during which time 15 plasma exchanges were performed. Plasma was assayed for vidarabine and its principal metabolite, hypoxanthine arabinoside by high pressure liquid chromatography. Vidarabine was not detected in the plasma of any patients. Hypoxanthine arabinoside levels were used to evaluate vidarabine kinetics. The serum levels of hypoxanthine arabinoside ranged from 3.6 to 21.5 mg/l. The mean elimination half-life (+/- SD) was 3.0 +/- 1.7 h. The plasma clearance (mean +/- SD) was 195 +/- 270 ml/min when the dose was 7.5 mg/kg per day and 66.3 +/- 47 ml/min for a 15 mg/kg per day/dose (NS). Except for the elimination half-life, these results were not fully consistent with those observed in other studies. The influence of multiple plasma exchanges on vidarabine kinetics is limited and dosage adjustment is not required based on the continuous infusion of vidarabine.
Topics: Humans; Polyarteritis Nodosa; Vidarabine
PubMed: 1348236
DOI: 10.1111/j.1472-8206.1992.tb00088.x