title: In vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu) and active metabolite.
abstract: Neuropsychiatric adverse events have been reported in influenza patients with and without exposure to oseltamivir (Tamiflu), triggering speculation as to whether oseltamivir may be interacting with any human receptors and contributing to such neuropsychiatric events. In this study, the in vitro selectivity profile of oseltamivir prodrug and active metabolite was investigated. Both compounds lacked clinically relevant pharmacological activities on human, rodent and primate neuraminidases and on a panel of 155 other molecular targets, including those relevant for mood, cognition and behavior. Neuropsychiatric adverse events observed in influenza patients are likely a phenomenon caused by the infection rather than by oseltamivir.
authors.affiliation: Discovery Neuroscience, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Lothar
authors.initials: L
authors.lastname: Lindemann
authors.forename: Helmut
authors.initials: H
authors.lastname: Jacobsen
authors.forename: Diana
authors.initials: D
authors.lastname: Schuhbauer
authors.forename: Frederic
authors.initials: F
authors.lastname: Knoflach
authors.forename: Silvia
authors.initials: S
authors.lastname: Gatti
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Wettstein
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Loetscher
authors.forename: Tom
authors.initials: T
authors.lastname: Chu
authors.forename: Martin
authors.initials: M
authors.lastname: Ebeling
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.forename: Eric
authors.initials: E
authors.lastname: Prinssen
authors.forename: Manfred
authors.initials: M
authors.lastname: Brockhaus
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000201:enzymology; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D053139:Oseltamivir / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010710:Phosphates / Q000737:chemistry; D011323:Primates / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D013379:Substrate Specificity
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D010710:Phosphates; D011355:Prodrugs; D053139:Oseltamivir; D009439:Neuraminidase; C535162:oseltamivir carboxylate