Comparison of the anti-respiratory syncytial virus activity and toxicity of papaverine hydrochloride and pyrazofurin in vitro and in vivo.
Based on reports describing their broad antiviral activity, the toxicity and antiviral efficacy of papaverine hydrochloride and pyrazofurin against respiratory syncytial virus (RSV) infection were tested in vitro in tissue culture cells and in vivo in cotton rats. Papaverine inhibited RSV replication in vitro; however, the median minimal toxic dose-median minimal inhibitory concentration ratios (MTD50:MIC50) in vitro and in vivo for papaverine were less than 4. Further work with this compound was discontinued. In contrast, pyrazofurin inhibited RSV replication in vitro (a mean MIC50 of 0.04 microgram/ml was obtained) and in vivo (RSV pulmonary titers were significantly reduced consistently in cotton rats given daily 10 mg/kg doses compared to untreated control animals). However, some toxic effects were observed in both the in vitro and in vivo tests of this compound. The remaining potential of pyrazofurin as an anti-RSV compound is discussed.
Wyde
P R
PR
Department of Microbiology, Baylor College of Medicine, Houston, Texas 77030.
Gilbert
B E
BE
Ambrose
M W
MW
D000577:Amides; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D003411:Arvicolinae; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D009297:Nasal Mucosa / Q000382:microbiology; D010208:Papaverine / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011720:Pyrazoles; D051381:Rats; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D010253:Respirovirus Infections / Q000188:drug therapy*; D012263:Ribonucleosides / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D012266:Ribose; D014779:Virus Replication / Q000187:drug effects
D000577:Amides; D000998:Antiviral Agents; D011720:Pyrazoles; D012263:Ribonucleosides; C002997:pyrazofurin; D012266:Ribose; D010208:Papaverine