title: 8-Aminoquinolines from Walter Reed Army Institute for Research for treatment and prophylaxis of Pneumocystis pneumonia in rat models.
abstract: 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.
authors.affiliation: Indiana University School of Medicine, Indianapolis 46202-5120.
authors.forename: M S
authors.initials: MS
authors.lastname: Bartlett
authors.forename: S F
authors.initials: SF
authors.lastname: Queener
authors.forename: R R
authors.initials: RR
authors.lastname: Tidwell
authors.forename: W K
authors.initials: WK
authors.lastname: Milhous
authors.forename: J D
authors.initials: JD
authors.lastname: Berman
authors.forename: W Y
authors.initials: WY
authors.lastname: Ellis
authors.forename: J W
authors.initials: JW
authors.lastname: Smith
mesh_terms: 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
chemical_list: D000634:Aminoquinolines; D002981:Clindamycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011319:Primaquine