Some selective serotonin reuptake inhibitors inhibit dynamin I guanosine triphosphatase (GTPase)

Masahiro Otomo, Kiyofumi Takahashi, Hiroshi Miyoshi*, Kenichi Osada, Hideki Nakashima, Noboru Yamaguchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Neuronal dynamin I plays a critical role in the recycling of synaptic vesicles, and thus in nervous system function. We expressed and purified dynamin I to explore potentially clinically useful endocytosis inhibitors and to examine the mechanism of their action. We estimated the IC50 of nineteen psychotropic drugs for dynamin I. The IC50 values of two selective serotonin reuptake inhibitors (sertraline and fluvoxamine) were 7.3±1.0 and 14.7±1.6 μM, respectively. Kinetic analyses revealed that fluvoxamine is a noncompetitive inhibitor of dynamin I guanosine triphosphatase (GTPase) with respect to guanosine 5′-triphosphate (GTP) and a competitive inhibitor with respect to L-phosphatidylserine (PS). Fluvoxamine may compete with PS for binding to the pleckstrin homology domain of dynamin I. On the other hand, sertraline was a mixed type inhibitor with respect to both GTP and PS. Our results indicate that sertraline and fluvoxamine may regulate the transportation of neurotransmitters by modulating synaptic vesicle endocytosis via the inhibition of dynamin I GTPase.

Original languageEnglish
Pages (from-to)1489-1495
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Issue number8
Publication statusPublished - 2008 Aug
Externally publishedYes


  • Dynamin
  • Endocytosis
  • Guanosine triphosphatase
  • Inhibitor
  • Selective serotonin reuptake inhibitor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)


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