SIGMAR1 binds fluvoxamine

Stable Identifier
Reaction [binding]
Homo sapiens
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Among selective serotonin reuptake inhibitors (SSRIs), fluvoxamine shows high affinity for sigma-1 receptors (SIGMAR1). Binding (Ishikawa et al. 2007) and stimulation of SIGMAR1 by fluvoxamine elicits antidepressive effects in rats (Yagasaki et al. 2006, Fishback et al. 2010). The endogenous ligand for SIGMAR1 may be progesterone (Ganapathy et al. 1999). Small anecdotal studies suggest that ligands that target SIGMAR1 may be useful in treating central hypoventilation syndromes (Loiseau et al. 2018), suggesting a possible role for such drugs in treatment of COVID-19 symptoms. After several trials for the use of fluvoxamine the US FDA rejected an Emergency
Use Authorization of Fluvoxamine, giving a detailed summary of results (FDA, 2022).

Literature References
PubMed ID Title Journal Year
16522641 Chronic antidepressants potentiate via sigma-1 receptors the brain-derived neurotrophic factor-induced signaling for glutamate release

Hayashi, T, Kunugi, H, Yagasaki, Y, Numakawa, T, Kumamaru, E, Su, TP

J. Biol. Chem. 2006
23641311 From α4β2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design

Zhang, HK, Gunosewoyo, H, Kozikowski, AP, Yu, LF

ACS Med Chem Lett 2012
  Memorandum Explaining Basis for Declining Request for Emergency Use Authorization of Fluvoxamine Maleate

Food and Drug Administration, FDA

17662961 High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503

Ishii, K, Fujisaki, M, Hashimoto, K, Iyo, M, Shirayama, Y, Ishiwata, K, Naganawa, M, Ishikawa, M, Shimizu, E, Oda, K, Kimura, Y, Miyatake, R, Sakata, M

Biol. Psychiatry 2007
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