A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia VIRUS and varicella zoster virus. [PubChem]
Indication
For treatment of chickenpox - varicella, herpes zoster and herpes simplex
Pharmacology
Vidarabine is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of Vidarabine is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts Vidarabine into Vidarabine monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. in vitro, Vidarabine triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, Vidarabine triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where Vidarabine triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand.
Toxicity
Acute massive overdosage by oral ingestion of the ophthalmic ointment has not occurred. However, the rapid deamination to arabinosylhypoxanthine should preclude any difficulty. The oral LD50 for vidarabine is greater than 5020 mg/kg in mice and rats. No untoward effects should result from ingestion of the entire contents of the tube. Overdosage by ocular instillation is unlikely because any excess should be quickly expelled from the conjunctival sac.
Affected Organisms
Human Herpes Virus
Biotransformation
In laboratory animals, vidarabine is rapidly deaminated in the gastrointestinal tract to Ara-Hx.
Absorption
Systemetic absorption of vidarabine should not be expected to occur following ocular administration and swallowing lacrimal secretions.
Research Area: Infection Biological Activity: Vidarabine(Vira-A) is an antiviral drug which is active against herpes simplex and varicella zoster viruses. Vidarabine works by interfering with the synthesis of viral DNA. It is a nucleoside analog, therefore it has to be phosphorylated and to be active. Vidarabine stops replication of herpes viral DNA in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, 3) inactivation of the viral DNA polymerase. [1]
Application Used to study the roles of AMP-activated protein kinase (AMPK) in cell signaling. Biochem/physiol Actions Cell-permeable adenylate cyclase inhibitor; in detergent-dispersed rat brain preparation, IC50 = 30 μM. Clinically significant antiviral agent, especially against herpes simplex (HSV),1 by inhibition of DNA polymerase.
Biochem/physiol Actions Cell-permeable adenylate cyclase inhibitor; in detergent-dispersed rat brain preparation, IC50 = 30 μM. Clinically significant antiviral agent, especially against herpes simplex (HSV),1 by inhibition of DNA polymerase.
有害性 (Xn)