Antimalarial activities and subacute toxicity of RC-12, a 4-amino-substituted pyrocatechol.
RC-12 [1,2-dimethoxy-4-(bis-diethylaminoethyl)-amino-5-bromobenzene] was evaluated for prophylactic, radical curative, and suppressive activities against infections with Plasmodium cynomolgi and subacute toxicity in rhesus monkeys. Applied as a prophylactic agent, RC-12, administered in doses of 6.25 to 25.0 mg/kg daily throughout the incubation period, provided near-complete to complete protection against 10(5) to 10(6) times the minimum infective dose of sporozoites. Applied as a suppressive agent, daily doses of 100.0 mg of RC-12 per kg did not eradicate blood schizonts regularly; hence, the need for concomitant administration of a blood schizonticide, such as chloroquine, in assessments of radical curative activity. In such appraisals, daily doses of 6.25 to 25.0 mg of RC-12 per kg for 14 days, in combination with 2.5 mg of chloroquine per kg daily for 7 days, effected cure of 69 and 93% of established infections, respectively. The curative activity of RC-12 was related to the total dose and could be achieved with a regimen as brief as 4 days. With respect to outward expressions of toxicity, daily doses of 50.0 mg/kg or lower for 15 to 225 days evoked no reactions. Doses of 100.0 or 200.0 mg/kg, scheduled for 15 days, evoked convulsions and depression and were, respectively, lethal to 4 of 17 and 7 of 7 recipients. Doses of 25.0 mg/kg or lower evoked no discrete reactions. Doses of 50.0 mg/kg and higher evoked hepatomegaly, vacuolation of hepatocytes, and elevations of glutamic oxalacetic and glutamic pyruvic transferase activities in serum, reactions related in intensity to dose but not duration of dosage.
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D004352:Drug Resistance, Microbial; D005029:Ethylenediamines / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D008253:Macaca mulatta; D008288:Malaria / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D010961:Plasmodium / Q000187:drug effects; D013997:Time Factors
D000962:Antimalarials; D005029:Ethylenediamines; C006018:RC-12; D001219:Aspartate Aminotransferases