Antiviral effect of 1-morpholinomethyl-tetrahydro-2(1H)-pyrimidinone (DD-13) in experimental alphaviral infections in white mice.
1-Morpholinomethyl-tetrahydro-2(1H)-pyrimidinone (DD-13), a selective inhibitor of the alphaviral reproduction in vitro, manifests a pronounced antiviral activity in experimental infections with Semliki forest virus (SFV) and Sindbis virus in white mice (intraperitoneally inoculated with 10-10 000 LD50). Introduced subcutaneously in mice infected with SFV the compound was effective within the dose range of 4.7-300 mg/kg. The effective dose (ED)50 value of DD-13 is about 18.7 mg/kg and the maximum effect is reached with a 150-300 mg/kg dose. The protection index reached 80% and the mean survival time from approximately 7 days in the placebo group was lengthened to 26 days. This high antiviral effect is distinguished by its high selectivity, the selectivity ratio (LD50/ED50) being 385 (LD50 = 7200 mg/kg) and is manifested in infections with massive viral inocula (100-1000 LD50). The effective treatment schedule was determined: two divided daily doses of 37.5-150 mg/kg, beginning on the 3rd day after infection to the 8th day. After intravenous administration of DD-13 in mice infected with SFV a high protective effect was also observed, which was equal to that of the subcutaneous application, but with doses several times lower: in the 3-40 mg/kg. ED50 is about 3.5 mg/kg and the optimal effective dose is 10-20 mg/kg, i.e. 1/12-1/6 of LD50 (116 mg/kg). The selectivity ratio is about 33. The most effective treatment course is accomplished by a 10-20 mg/kg daily dose (in two applications) starting on the 2nd day after the virus inoculation up to the 8th day.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D051379:Mice; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012672:Semliki forest virus; D012845:Sindbis Virus; D013997:Time Factors; D014036:Togaviridae Infections / Q000188:drug therapy*
D000998:Antiviral Agents; D011744:Pyrimidinones; C047314:1-morpholinomethyl-tetrahydro-1(1H)-pyrimidinone