Diamidines for human African trypanosomiasis.
Aromatic diamidines are potent trypanocides. Pentamidine, a diamidine, has been used for more than 60 years to treat human African trypanosomiasis (HAT); however, the drug must be administered parenterally and is active against first-stage HAT only, prior to the parasites causing neurological deterioration through invasion of the CNS. A major research effort to design novel diamidines has led to the development of orally active prodrugs and, remarkably, a new generation of compounds that can penetrate the CNS. In this review, progress in the development of diamidines for the treatment of HAT is discussed.
Paine
Mary F
MF
University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, Campus Box 7569, and Department of Pathology and Laboratory Medicine, Campus Box 7525, Chapel Hill, NC 27599, USA
Wang
Michael Zhuo
MZ
Generaux
Claudia N
CN
Boykin
David W
DW
Wilson
W David
WD
De Koning
Harry P
HP
Olson
Carol A
CA
Pohlig
Gabriele
G
Burri
Christian
C
Brun
Reto
R
Murilla
Grace A
GA
Thuita
John K
JK
Barrett
Michael P
MP
Tidwell
Richard R
RR
D000818:Animals; D001550:Benzamidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002986:Clinical Trials as Topic; D015195:Drug Design; D004351:Drug Resistance; D006801:Humans; D010419:Pentamidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
D001550:Benzamidines; D011355:Prodrugs; D014344:Trypanocidal Agents; D010419:Pentamidine; C458513:pafuramidine