Chemotherapy of Leishmaniasis.
Final rept. 1 Jul 74-30 Sep 84,
GEORGIA UNIV RESEARCH FOUNDATION INC ATHENS
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A total of 3,746 compounds was tested for antileishmanial activity against three day infections of Leishmania donovani in golden hamsters. Twelve hundred fifty-three of these were significantly active 220 had activity greater than the reference compound, meglumine antimoniate Glucantime G indexes ranged from 1.53 to 700.00. Using various modifications of this test system to optimize the treatment regimen of selected promising compounds, the efficacy of Glucantime, WR06026, or formycin B was similar when administered in a single treatment, or in 2, a4, 8, or 16 treatments. These three compounds were highly efficacious but not curative when used alone, or in combination against visceral leishmaniasis. A total of 734 compounds was tested for antileishmanial activity against nineteen day infections of Leishmania braziliensis panamensis in golden hamsters. Using various modifications of the visceral or cutaneous leishmaniasis test systems, the antileishmanial efficacy of a total of 231 liposome preparations liposome-encapsulated antimonial drugs or 8-aminoquinolines was evaluated 225 against L. donovani and 6 against L. b. panamensis. Treatment of L. donovani infections in hamsters with incremental increases of Glucantime resulted in parasites resistant to dosage levels of Glucantime as high as 824 mgkgday MKD. Dogs, owl monkeys, squirrel monkeys, and opossums were evaluated as animal models of visceral leishmaniasis and each species was determined useful for preclinical testing of promising antileishmanial drugs.
- Medicine and Medical Research