Description
Norfluoxetine is an active metabolite of the antidepressant fluoxetine. It is formed from fluoxetine by the cytochrome P450 (CYP) isoforms CYP2C9, CYP2C19, and CYP3A. Norfluoxetine inhibits serotonin (5-HT) uptake in rat brain synaptosomal membrane preparations (K
i = 44.7 nM) and isolated human platelets (IC
50 = ~15 nM). It has been found in the tissues of fish exposed to wastewater effluent.
Chemical Properties
NORFLUOXETINE HYDROCHLORIDE is Light Beige to Light Brown Solid
Uses
Norfluoxetine Hydrochloride is a metabolite of Fluoxetine (F597100), a selective serotonin reuptake inhibitor which is used as an antidepressant.
Uses
Norfluoxetine hydrochloride has been used to examine if psychoactive pharmaceuticals in drinking water at environmental concentrations could induce neuronal gene expression. It has also been used to examine whether at environmental concentrations it can alter
in vitro expression of autism spectrum disorders (ASD)-associated synaptic proteins in human neurons.
Biochem/physiol Actions
Norfluoxetine is an active metabolite of fluoxetine. It disturbs the production of estrogen in a co-culture model of the feto-placental unit.
in vivo
Pretreatment with Fluoxetine or Norfluoxetine hydrochloride (20mg/kg s.c.), as well as Phenytoin (30 mg/kg s.c.) and Clonazepam (0.1mg/kg s.c.) significantly increases both the rate and duration of survival, demonstrating a significant protective effect against Pentylenetetrazol-induced epilepsy[1].
IC 50
5-HT Receptor; Ca
V3.3: 5 μM (IC
50)
References
[1] CHRISTIAAN C VEERMAN. Slow delayed rectifier potassium current blockade contributes importantly to drug-induced long QT syndrome.[J]. Circulation. Arrhythmia and electrophysiology, 2013, 6 5: 1002-1009. DOI:
10.1161/circep.113.000239[2] JUSTIN D LUTZ. Stereoselective inhibition of CYP2C19 and CYP3A4 by fluoxetine and its metabolite: implications for risk assessment of multiple time-dependent inhibitor systems.[J]. Drug Metabolism and Disposition, 2013, 41 12: 2056-2065. DOI:
10.1124/dmd.113.052639[3] DAVID T. WONG PH.D. Norfluoxetine Enantiomers as Inhibitors of Serotonin Uptake in Rat Brain[J]. Neuropsychopharmacology, 1993, 8 4: 337-344. DOI:
10.1038/npp.1993.33[4] JUN ZUO. Fluoxetine is a potent inhibitor of coxsackievirus replication.[J]. Antimicrobial Agents and Chemotherapy, 2012, 56 9: 4838-4844. DOI:
10.1128/aac.00983-12[5] CONOR MCCLENAGHAN. Polymodal activation of the TREK-2 K2P channel produces structurally distinct open states.[J]. Journal of General Physiology, 2016, 147 6: 497-505. DOI:
10.1085/jgp.201611601
