ABSTRACT
A series of anthraquinones with amino substituents at the 1,5 positions were found to induce interferon in mice. A prototype compound, 1,5-bis[(3-morpholinopropyl)amino]-anthraquinone (Ia), was an effective antiviral agent when administered either orally or parenterally. Peak interferon titers were found 12 to 24 h after drug treatment. The minimum oral dose of Ia required to induce serum interferon or to protect mice against a lethal virus infection was 62 mg/kg. Mice tolerated an oral dose of at least 30 times this minimum effective dose. A single dose of Ia given up to 6 days prior to infection had significant protective activity. Biological properties of Ia were compared with those of three other 1,5-diamino anthraquinones, which also induced interferon and demonstrated antiviral activity in mice. The most active compound was 1,5-bis[[2-(diethylamino)ethyl]amino]-anthraquinone (Ib), which protected mice against virus infection at a dose as low as 8 mg/kg (less than 1/60 its maximum tolerated dose). Mice developed hyporeactivity to interferon induction if the same inducer was injected daily, although by alternating between different inducers the loss of interferon responsiveness could be avoided.
Subject(s)
Anthraquinones/pharmacology , Antiviral Agents , Interferon Inducers , Animals , Dose-Response Relationship, Drug , Horses , Humans , Interferons/blood , MiceABSTRACT
5,6-Dihydro-5-azathymidine, administered subcutaneously, was active both prophylactically and therapeutically against cutaneous herpesvirus infection of hairless mice. Activity was comparable to that obtained with adenine arabinoside.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Herpes Simplex/drug therapy , Skin Diseases, Infectious/drug therapy , Thymidine/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , Male , Mice , Mice, Inbred Strains , Thymidine/pharmacologyABSTRACT
2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166) induced high levels of circulating interferon in mice when administered either parenterally or orally. Peak titers of interferon were found in the serum between 6 and 12 h after inoculation of the drug. Lower but significant levels of interferon were found in rat serum after administration of U-25,166 by either the intraperitoneal or oral route, and good levels of circulating interferon were observed in cats after oral treatment. Repeated intraperitoneal doses (50 mg/kg) of U-25,166 protected mice against intranasal encephalomyocarditis virus challenge. The minimal effective acute oral dose for antiviral activity was approximately 250 mg/kg. This was also the minimal dose that produced detectable levels of interferon. Maximum tolerated doses in mice were four to six times the minimal effective doses. A single oral treatment was protective in mice against challenge virus inoculated 24 h later. The compound protected mice from challenge with high levels of encephalomyocarditis virus, up to 20,000 mean lethal doses. Antiviral activity in mice was retained when certain minor substitutions were made in the U-25,166 structure.
Subject(s)
Enterovirus Infections/prevention & control , Interferon Inducers , Interferons/blood , Pyrimidines/pharmacology , Administration, Oral , Animals , Cats , Chemical Phenomena , Chemistry , Drug Evaluation, Preclinical , Encephalomyocarditis virus , Injections, Intraperitoneal , Interferon Inducers/therapeutic use , Lethal Dose 50 , Mice , Pyrimidines/therapeutic use , RatsABSTRACT
Passively immunized hairless mice were inoculated cutaneously with herpes simplex virus. Thirty-nine days later, when the primary cutaneous lesions had completely healed, the mice were treated subcutaneously with prednisone. Within 12 to 30 days after starting prednisone treatment, herpesvirus was recovered by skin swabs from 12 of 71 (17%) of the treated mice. This new model has potential application for understanding and treating recurrent cutaneous herpes infections.
Subject(s)
Herpes Simplex , Simplexvirus/isolation & purification , Animals , Culture Techniques , Cytopathogenic Effect, Viral , Disease Models, Animal , Hair/abnormalities , Herpes Simplex/microbiology , Hydrocortisone/pharmacology , Immune Sera , Immunity, Maternally-Acquired , Kidney , Male , Mice , Mice, Inbred Strains , Prednisone/pharmacology , Rabbits/immunology , Recurrence , Viral Plaque Assay , Virus CultivationABSTRACT
A 2.5% preparation of kethoxal in cream was compared with the cream placebo for efficacy against cutaneous herpes simplex in a double-blind clinical study. The kethoxal formulation was not significantly more effective than the placebo. This conclusion was based on subjective impressions of the patients, observations by the physicians, and quantitative measurement of herpesvirus recovered from the lesions. It was suggested that the lack of clinical activity, in contrast to the marked activity against experimental infections in laboratory animals, resulted from the fact that high levels of herpesvirus were already present in the skin before symptoms were noted.
