Target-Organ Treatment of Neurotropic Virus Diseases: Efficacy as a Chemotherapy Tool and Comparison of Activity of Adenine Arabinoside, Cytosine Arabinoside, Idoxuridine, and Trifluorothymidine

Anti-deoxyribonucleic acid virus activities of 3′- O -acyl derivatives of 2,2′-anhydro-1-β- d -arabinofuranosyl cytosine (cyclo-C) and 1-β- d -arabinofuranosylcytosine (Ara-C) were evaluated by using an in vivo test system in mice. Among the derivatives tested, 3′- O -decanoyl cyclo-C hydrochloride was the most effective against herpes simplex virus-induced encephalitis in mice when the drug was administered directly into infected brains of mice (target-organ treatment). A comparative study of the treatment of herpetic encephalitis in mice with 3′ O -decanoyl cyclo-C and other nucleosides, including Ara-C, 9-β- d -arabinofuranosyladenine (Ara-A), and 5-iodo-2′-deoxyrudine (IUdR), proved Ara-A to be more efficacious than the other nucleosides, followed by 3′- O -decanoyl cyclo-C, which was more active than Ara-C and IUdR. Administration of 3′- O -acyl cyclo-C's by intraperitoneal injection, however, failed to demonstrate activity against herpetic encephalitis in mice. The antivaccinial activity of 3′- O -decanoyl cyclo-C was also compared with that of other compounds against encephalitis and dermal tail lesions in mice caused by vaccinia virus infection. Interaperitoneally administered 3′- O -decanoyl cyclo-C and Ara-C also showed no significant activity against the diseases. Under these test conditions, N -methylisatin-β-thiosemicarbazone (Marboran) was the most active compound, followed by Ara-A.

Section: Resultsmentioning

confidence: 99%

“…The experiment procedure for target-organ treatment was essentially that of Allen and Sidwell (1), except that 30 LD50 of the HF strain of HSV in 0.025 ml of solution containing the drug to be tested was directly inoculated into the brains of mice.…”

mentioning

confidence: 99%

Comparative Study of the Antiviral Activity of Acyl Derivatives of 2,2′-Anhydro-1-β- d -Arabinofuranosylcytosine and Other Nucleosides Against Encephalitis in Mice

Nishiyama

Sato

Yamanaka

et al. 1977

“…In these studies the maximum tolerated dose (MTD) or maximum obtainable dose (MOD), or a fraction thereof, was tested. The insolubility of ara-A necessitated the use of a saturated solution (2), which resulted in an MOD of -2.5 mg/kg. Virus control mice received an i.c.…”

mentioning

confidence: 99%

“…In the i.c. (target organ) studies, each drug in saline (0.03 ml) was injected 6 h after virus inoculation (2). In these studies the maximum tolerated dose (MTD) or maximum obtainable dose (MOD), or a fraction thereof, was tested.…”

mentioning

confidence: 99%

Inhibition of Experimental Deoxyribonucleic Acid Virus-Induced Encephalitis by 9-β- d -Arabinofuranosylhypoxanthine 5′-Monophosphate

Allen¹,

Thompson²,

Huffman³

et al. 1975

Self Cite

9-β- d -Arabinofuranosylhypoxanthine 5′-monophosphate (ara-HxMP) significantly controlled the development of encephalitis produced by deoxyribonucleic acid viruses in mice. In most experiments the activities of ara-HxMP and 9-β- d -arabinofuranosyladenine (ara-A) were determined simultaneously. In the intracerebral (target organ) and intravenous therapy experiments, ara-HxMP had a pronounced advantage over ara-A since the water solubility of ara-HxMP enabled it to be used in much higher concentrations. In experiments where the two drugs were administered intraperitoneally or orally they exhibited similar activity. In several intraperitoneal therapy experiments ara-HxMP was tested alone, using various treatment schedules and dosages. In these experiments, efficacy was observed in groups that had treatments initiated as late as 72 h after virus inoculation.

“…Ether-anesthetized mice (-20 g) were infected i.c. with -2 mean lethal doses of HV/1 (strain 123) as described previously (1). The drug was administered as a single i.c.…”

mentioning

confidence: 99%

Antiviral Activity of 3-Deazaguanine, 3-Deazaguanosine, and 3-Deazaguanylic Acid

Allen¹,

Huffman²,

Cook³

et al. 1977

Self Cite

3-Deazaguanine (ICN 4221), 3-deazaguanosine (ICN 4793), and 3-deazaguanylic acid (ICN 5412) represent a new class of synthetic guanine analogs having antiviral activity. In vitro, nine ribonucleic acid and seven deoxyribonucleic acid viruses were inhibited, including influenza, parainfluenza, rhino-, vesicular stomatitis, adeno-, herpes-, cytomegalo-, vaccinia, pseudorabies, and myxoma viruses. They were effective orally against influenza types A and B and parainfluenza type 1 (Sendai) virus infections in mice, with a therapeutic index of 16 against the latter two viruses. The course ofherpes encephalitis was altered only when the drugs were applied directly into the brain. In addition, these drugs were effective inhibitors of Friend leukemia virus-induced splenomegaly in mice; treatment also produced extensions of life in these animals.