Arachidonic Acid Mimics
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) inhibit the oxidation of arachidonic acid by COX (= PGHS), and it is believed that their analgesic and anti-inflammatory properties are at least partially due to this. The competitive inhibition of COX by arylpropionic and arylacetic acid derivatives is based on their molecular mimicry of arachidonic acid. Since arachidonic acid derivatives were discovered to be endogeneous cannabis receptor ligands, we have cooperated with other reserach groups, researching the likely possibility that known COX inhibitory NSAIDs interact with the endocannabinoid system. We extended this hypothesis to drugs that get acylated metabolically with arachidonic acid. We were able to identify two arachidonic acid amides as new metabolites of the well-known potent analgesic metamizol (dipyrone), characterising them pharmacologically.
Cooperations:
Prof. Dr. Vincenzo Di Marzo and Dr. Luciano De Petrocellis, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy
Dr. Aron H. Lichtman, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
Bernhard Watzer, Mutter-Kind-Zentrum, Zentrum für Kinder- und Jugendmedizin, Pädiatrische Forschung, Labor für Instrumentelle Analytik, Marburg
Prof. Dr. Rolf Nüsing, Pharmazentrum Frankfurt, Institut für Klinische Pharmakologie, Frankfurt/M.
PD Dr. Matthias Dollinger and Dr. Jens Walldorf, Universitätsklinik und Poliklinik für Innere Medizin I, Martin-Luther-Universität, Halle
Alexander Zörner, Project Manager Pharmacovigilance, Institut für Klinische Pharmakologie, Medizinische Hochschule Hannover
PhD and Diploma Theses:
M. Graf, Diploma Thesis (Pharmazie) Halle 1999
T. Rogosch, Diploma Thesis (Pharmazie) Halle 2003
T. Rogosch, PhD Thesis Marburg 2005
C. Sinning, PhD Thesis Halle 2008
L. Radanova, PhD Thesis, in preparation, Halle 2013
Publications:
P. Imming, M. Graf, S. Tries, R. Hirschel, E. Krause, G. Pawlitzki, anti-inflammatory Planar Chiral [2.2] paracyclophanes Acetic Acid enantiomer. Inflamm. Res 2001, 50, 371-374.
M. Lämmerhofer, P. Imming, W. Lindner, Direct High-Performance Liquid Chromatographic Enantiomer Separation of anti-inflammatory Planar Chiral [2.2] paracyclophane-4-acetic Acid. Chromatographia 2004, 59, 1-5.
C. Sinning, B. Watzer, L. De Petrocellis, V. Di Marzo, P. Imming, Dopamides, Vanillylamides, Ethanolamides, and Arachidonic Acid Amides of Anti-inflammatory and Analgesic Drug Substances as TRPV1 Ligands. ChemMedChem 2008, 3, 1956-1964. doi:10.1002/cmdc.200800271
C. Sinning, B. Watzer, O. Coste, R. M. Nüsing, I. Ott, A. Ligresti, V. Di Marzo, P. Imming, New Analgesics Synthetically Derived from the Paracetamol Metabolite N-(4-hydroxyphenyl) - (5Z, 8Z, 11Z, 14Z)-icosatetra 5,8,11,14-enamides. J Med Chem 2008, 51, 7800-7805. doi:10.1021/jm800807k
T. Rogosch, C. Sinning, A. Podlewski, B. Watzer, J. Schlosburg, A. H. Lichtman, M. G. Cascio, T. Bisogno, V. Di Marzo, R. Nüsing, P. Imming, Novel bioactive metabolites of dipyrone (metamizole ). Bioorg. Med Chem 2012, 20, 101-107. doi:10.1016/j.bmc.2011.11.028
J. E. Schlosburg, L. Radanova, V. Di Marzo, P. Imming, A. H. Lichtman, Evaluation of the endogenous cannabinoid system in mediating the behavioral effects of dipyrone (metamizol) in mice. Behav. Pharmacol. 2012, 23, 722-726. doi:10.1097/FBP.0b013e3283584794
S. Maione, L. Radanova, D. De Gregorio, L. Luongo, L. De Petrocellis, V. Di Marzo, P. Imming, Effects of metabolites of the analgesic agent dipyrone (metamizol) on rostral ventromedial medulla cell activity in mice. Eur. J. Pharmacol. 2015, 748, 115-122. doi:10.1016/j.ejphar.2014.12.022