In vitro pharmacological selectivity profile of oseltamivir prodrug (Tamiflu ®) and active metabolite

• Published in: European journal of pharmacology Vol. 628; no. 1; pp. 6 - 10
• Main Authors: Lindemann, Lothar, Jacobsen, Helmut, Schuhbauer, Diana, Knoflach, Frederic, Gatti, Silvia, Wettstein, Joseph G., Loetscher, Hansruedi, Chu, Tom, Ebeling, Martin, Paulson, James C., Prinssen, Eric, Brockhaus, Manfred
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.02.2010; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Human viral diseases; Humans; Infectious diseases; Influenza; Influenza A Virus, H3N2 Subtype - enzymology; Medical sciences; Neuraminidase; Neuraminidase - antagonists & inhibitors; Neuraminidase - metabolism; Neuropsychiatric adverse event; Oseltamivir; Oseltamivir - analogs & derivatives; Oseltamivir - chemistry; Oseltamivir - metabolism; Oseltamivir - pharmacology; Pharmacology. Drug treatments; Phosphates - chemistry; Primates; Primates - metabolism; Prodrugs - chemistry; Prodrugs - metabolism; Prodrugs - pharmacology; Rats; Selectivity; Substrate Specificity; Tamiflu; Toxicity: nervous system and muscle; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Oseltamivir; Selectivity; Tamiflu; Influenza; Neuraminidase; Neuropsychiatric adverse event; Neuraminidase inhibitor; Enzyme; Metabolite; Toxicity; Enzyme inhibitor; Prodrug; In vitro; Glycosylases; Infection; Glycosidases; Viral disease; Exo-α-sialidase; Secondary effect; Mental disorder; Hydrolases; Antiviral
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.11.020

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.