In vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu) and active metabolite.
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.
Lindemann
Lothar
L
Discovery Neuroscience, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Jacobsen
Helmut
H
Schuhbauer
Diana
D
Knoflach
Frederic
F
Gatti
Silvia
S
Wettstein
Joseph G
JG
Loetscher
Hansruedi
H
Chu
Tom
T
Ebeling
Martin
M
Paulson
James C
JC
Prinssen
Eric
E
Brockhaus
Manfred
M
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
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D010710:Phosphates; D011355:Prodrugs; D053139:Oseltamivir; D009439:Neuraminidase; C535162:oseltamivir carboxylate