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Journal of Virology, January 2006, p. 1044-1046, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.1044-1046.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mefloquine, an Antimalaria Drug with Antiprion Activity In Vitro, Lacks Activity In Vivo

David A. Kocisko1* and Byron Caughey1

National Institute of Allergy & Infectious Diseases, National Institutes of Health, Hamilton, Montana 598401

Received 25 August 2005/ Accepted 27 October 2005

In view of the effectiveness of antimalaria drugs inhibiting abnormal protease-resistant prion protein (PrP-res) 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 ~0.5 and ~1.2 µM, 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 PrP-res formation in vitro, many PrP-res inhibitors have no activity in vivo. This underscores the importance of testing promising candidates in vivo.

* Corresponding author. Mailing address: Rocky Mountain Laboratories, 903 S. 4th Street, Hamilton, MT 59840. Phone: (406) 375-9692. Fax: (406) 363-9286. E-mail: dkocisko{at}niaid.nih.gov.

Journal of Virology, January 2006, p. 1044-1046, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.1044-1046.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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