8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models.
Three 8-aminoquinolines from the Walter Reed Army Institute for Research (WRAIR), WR6026, WR238605, and WR242511, strongly inhibited Pneumocystis carinii growth in vitro at 1 microgram/ml. This activity was similar to that of primaquine. In rat therapy models, the WRAIR compounds affected Pneumocystis pneumonia at doses as low as 0.25 mg/kg (WR242511) or 0.5 mg/kg (WR6026 and WR238605). At these doses, primaquine alone was ineffective as therapy. In a rat prophylaxis model, all three WRAIR 8-aminoquinolines were extremely effective at daily doses of 0.57 mg/kg, showing activity greater than that of primaquine at this dosage and comparable to that of trimethoprim-sulfamethoxazole at 50/250 mg/kg.
Bartlett
M S
MS
Indiana University School of Medicine, Indianapolis 46202-5120.
Queener
S F
SF
Tidwell
R R
RR
Milhous
W K
WK
Berman
J D
JD
Ellis
W Y
WY
Smith
J W
JW
D000634:Aminoquinolines / Q000627:therapeutic use*; D000818:Animals; D002981:Clindamycin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D008168:Lung / Q000382:microbiology; D008297:Male; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D011319:Primaquine / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
D000634:Aminoquinolines; D002981:Clindamycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011319:Primaquine