NR ATXC
AU Kocisko,D.A.; Caughey,B.W.
TI Mefloquine, an antimalaria drug with antiprion activity in vitro, lacks activity in vivo
QU Journal of Virology 2006 Jan; 80(2): 1044-6
PT journal article
AB In view of the effectiveness of antimalaria drugs inhibiting abnormal protease-resistant prion protein (PrPres) formation in scrapie agent-infected cells, we tested other antimalarial compounds for similar activity. Mefloquine (MF), a quinoline antimalaria drug, was the most active compound tested against RML and 22L mouse scrapie agent-infected cells, with 50% inhibitory concentrations of approximately 0.5 and approximately 1.2 microM, respectively. However, MF administered to mice did not delay the onset of intraperitoneally inoculated scrapie agent, the result previously observed with quinacrine. While most anti-scrapie agent compounds inhibit PrPres formation in vitro, many PrPres inhibitors have no activity in vivo. This underscores the importance of testing promising candidates in vivo.
MH Animals; Antimalarials/administration & dosage/pharmacology; Drug Evaluation, Preclinical; Injections, Intraperitoneal; Mefloquine/*administration & dosage/pharmacology; Mice; Peptide Hydrolases/metabolism; *Prions/antagonists & inhibitors/metabolism; Research Support, N.I.H., Intramural; Research Support, U.S. Gov't, Non-P.H.S.; Scrapie/*prevention & control
AD National Institute of Allergy & Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. dkocisko@niaid.nih.gov
SP englisch
PO USA