Activity of quinfamide against natural infections of Entamoeba criceti in hamsters: a new potent agent for intestinal amoebiasis.
A novel tetrahydroquinolinyl ester, quinfamide, administered orally in multiple doses for 3 days had an ED50 of 0.25 mg/kg/day (total dose 0.75 mg/kg) for eradicating Entamoeba criceti in hamsters in several tests. It was significantly more active by direct comparison than 3 commercially available amoebicides and at least as active as 2 other esters of the parent compound, 1-(dichloroacety)-1,2,3,4-tetrahydro-6-quinolinol. After administration of a single dose, ED50 calculations for quinfamide averaged 0.9 mg/kg. Quinfamide was considerably more active than the other tetrahydroquinolinols, diloxanide furoate and teclozan, and it was approximately 1.5 times more active than etofamide; a statistical significance between the latter 2 drugs could be demonstrated in one of 4 tests. Administered prophylactically, quinfamide was shown to protect hamsters from re-infection with E. criceti. It also inhibited propagation of E. histolytica in vitro at a concentration of 20 microgram/ml. No adverse effects were noted in rodents after a single dose as high as 10 g/kg. Daily administration to monkeys of doses up to 500 mg/kg for as long as 37 days produced no pharmacological aberrations during or after medication; haematological studies and urine analyses were normal and no gross or microscopical tissue changes attributable to quinfamide were observed. No toxicity was revealed following acute (2 g/kg) and chronic (500 mg/kg/day x 31 days) administration of the drug to dogs and rats, respectively.
D000562:Amebiasis / Q000188:drug therapy*; D000563:Amebicides / Q000627:therapeutic use*; D000818:Animals; D006224:Cricetinae; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004748:Entamoeba histolytica / Q000187:drug effects; D004749:Entamoebiasis / Q000188:drug therapy*; D005260:Female; D008253:Macaca mulatta; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000563:Amebicides; D011804:Quinolines; C026546:quinfamide