ArticleBritish journal of pharmacology2013
Inhibition of MAO-A and stimulation of behavioural activities in mice by the inactive prodrug form of the anti-influenza agent oseltamivir.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Psychotic Agitation in a Patient with COVID-19: Pathogenesis or Iatrogenesis?Psychiatry and clinical psychopharmacology · 2021Article
- Article
- Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated KBritish journal of pharmacology · 2020Article
- MAO-A Inhibitory Potential of Terpene Constituents from Ginger Rhizomes-A Bioactivity Guided Fractionation.Molecules (Basel, Switzerland) · 2018Article
- The mechanisms of sudden-onset type adverse reactions to oseltamivir.Acta neurologica Scandinavica · 2017Review
- Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-International journal of Alzheimer's disease · 2017Article
- The mechanisms of delayed onset type adverse reactions to oseltamivir.Infectious diseases (London, England) · 2016Article
- Bakuchiol Is a Phenolic Isoprenoid with Novel Enantiomer-selective Anti-influenza A Virus Activity Involving Nrf2 Activation.The Journal of biological chemistry · 2015Article
- Task-specific enhancement of hippocampus-dependent learning in mice deficient in monoacylglycerol lipase, the major hydrolyzing enzyme of the endocannabinoid 2-arachidonoylglycerol.Frontiers in behavioral neuroscience · 2015Article
- A novel functional site in the PB2 subunit of influenza A virus essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication.The Journal of biological chemistry · 2014Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeOseltamivir is the most widely prescribed anti-influenza medication. However, in rare instances, it has been reported to stimulate behavioural activities in adolescents. The goal of this study was to determine the molecular mechanism responsible for these behavioural activities. EXPERIMENTAL APPROACH: We performed an in vitro assay of MAO-A, the enzyme responsible for neurotransmitter degradation, using either the active form - oseltamivir carboxylate (OC) or the inactive prodrug - oseltamivir ethyl ester (OEE). We also analysed the docking of MAO-A with OEE or OC in silico. Mouse behaviours after OEE or OC administration were monitored using automated video and computer analysis. KEY
resultsOEE, but not OC, competitively and selectively inhibited human MAO-A. The estimated Ki value was comparable with the Km values of native substrates of MAO-A. Docking simulations in silico based on the tertiary structure of MAO-A suggested that OEE could fit into the inner pocket of the enzyme. Behavioural monitoring using automated video analysis further revealed that OEE, not OC, significantly enhanced spontaneous behavioural activities in mice, such as jumping, rearing, sniffing, turning and walking. CONCLUSIONS AND IMPLICATIONS: Our multilevel analyses suggested OEE to be the cause of the side effects associated with oseltamivir and revealed the molecular mechanism underlying the stimulated behaviours induced by oseltamivir in some circumstances.
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