title: Parecoxib and its metabolite valdecoxib directly interact with cannabinoid binding sites in CB1-expressing HEK 293 cells and rat brain tissue.
abstract: Cyclooxygenase 2 inhibitors (COX 2) such as parecoxib (par) and valdecoxib (val) are used in the treatment of neuropathic pain. Using the radioligand binding assay it was demonstrated that both the prodrug par as well as its active metabolite val have a specific affinity to the cannabinoid (CB) receptor measured in CB1-expressing HEK 293 cells and rat brain tissue. Agonist activity was detected by GTPγS assays, cAMP formation experiments and ex vivo modulation of glutamate and GABA release of the rat brain tissue. In comparison to the specific cannabinoid agonist, WIN 55,212-2, the two COX 2 inhibitors are about 2 orders of magnitude less potent. The data suggest that the analgesic effects of par and its metabolite val in Wistar rats may be at least partially mediated by a direct interaction with the CB1 receptors. The COX 2 inhibitors appear to be a hypothetically useful tool for add-on therapy of neuropathic pain.
authors.affiliation: Department of Pharmacology & Toxicology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. helmut.schroeder@med.ovgu.de
authors.forename: Helmut
authors.initials: H
authors.lastname: Schröder
authors.forename: Volker
authors.initials: V
authors.lastname: Höllt
authors.forename: Axel
authors.initials: A
authors.lastname: Becker
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000096:biosynthesis; D003511:Cyclohexanols / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D014162:Transfection; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D000596:Amino Acids; D000242:Cyclic AMP; D003511:Cyclohexanols; D052246:Cyclooxygenase 2 Inhibitors; D018698:Glutamic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D007555:Isoxazoles; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides; D005680:gamma-Aminobutyric Acid; C406224:valdecoxib; D000096926:Benzenesulfonamides; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C409945:parecoxib