anti-inflammatoteand antimalarial activitie	In this study,
a fractionation of the crude extract, guided by the antinociceptive bioactivity, led to the isolation of a potent analgesic compound, which was identified as (±)-cis-2-[(dimethylami-
no)methy1]-1-(3-methoxyphenyl)cyclohexanol,	commonly
known by its international non-proprietary name (INN), tramadol. Tramadol was first manufactured by Griinenthal GmbH (Germany) and was brought into clinical usage in the late 1970s. It is now used worldwide for the treatment of
fractions F25 to F29, with a peak of activity in fraction F27 (Figure S1 b). F27 produced a dose-dependent (8, 16, or 32 mg kg-I, oral administration) inhibition of acetic-acidinduced abdominal constrictions on mice (Table SI). The mean 11350 value for oral administration of F27 was 14.1 mg kg-1 (55-41.9, at a 95% confidence limit) and the maximal inhibition was 56.8% [F(6, 78) = 101.42; p <0.001]. Naloxone partially antagonized the antinociceptive effect of this fraction (Figure S1 c). We further confirmed the analgesic
1*I A. Boumendje1,11 T. Chabrol, C. Beney, V. Sinniger, R. Haudecoeur,
F. Souard, A. Depaulis, 8. Bonn, M. De Waarel
Université Joseph Fourier, Grenoble (France)
E-mail: micheLdewaardeujfigrenoble.fr
A. Boumendje1,11 C. Beney, R. Haudecoeur, F. Souard
Unité CNRS 5063, Département de Pharmacochimie Moléculaire
Grenoble (France)
G. SotoingTeWe, T. Chabrol, V. Sinniger, A. Depaulis, B. Bonaz,
M. De Waardil
Unité Inserm U836, LabEx Ion Channels, Science and Therapeutics
Grenoble Institute of Neuroscience, Site Santé
38700 La Tronche (France)
C. Sotoing Tahve
Department of Zoology and Animal Physiology, University of Buea
P.O. Box 63, Buea (Cameroon)
G. Sotoing Taïwe
Department of Animal Biology and Physiology, Faculty of Science
University of Yaoundé I, P.O. Box 812, Yaoundé (Cameroon)
E. Ngo Bum
Department of Biological Science, University of Ngaoundere
Ngaoundere (Cameroon) L Marcourt, S. Challal, E. Ferreira Queiroz, J.-L. Wolfender
School of Pharmaceutical Sciences, University of Geneva
University of Lausanne, Geneva (Switzerland)
M. Le Borgne, T. Lomberget
Université de Lyon, Faculté de Pharmacie ISPB
EA 4446 B2C, 69373 Lyon (France)
C. Lavaud
Laboratoire de Pharmacognosie, Faculté de Pharmacie
Université de Reims, Reims (France)
R. Robins
UMR-C6230, Laboratoire CEISAM
Faculté des Sciences etTechniques, 44322 Nantes (France)
These authors contributed equally to this work.
M.D.W. thanks Inserm and LabEx Ion Channels, Science and
Therapeutics for financial support. M.L.B. and T.L. thank the ISPB of
Lyon for financial support. G.S.T. was funded by a PhD fellowship of
the Agence Française pour la Francophonie. A.B. thanks the Labex
ARCANE (ANR-11-LABX-0003-01) for financial support. We thank
Dr. G. Massiot for helpful discussions.
Supporting information for this article, including experimental
details, is available on the WWW under http://dx.doi.org/10.1002/
anie.201305697.
11780 Wiley Onfine Library	o 2013)	Click for Article Access Options	Angew. Chem. int. Ed. 2013, 52, 11780-11784