Norfluoxetine hydrochloride

Names

[ Name ]:
Norfluoxetine hydrochloride

[Synonym ]:
3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine,hydrochloride
Benzenepropanamine, γ-(4-(trifluoromethyl)phenoxy)-, hydrochloride
3-Phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1)
Benzenepropanamine, γ-[4-(trifluoromethyl)phenoxy]-, hydrochloride (1:1)

Biological Activity

[Description]:

Norfluoxetine hydrochloride is an active N-demethylated metabolite of Fluoxetine. Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor that is metabolized to Norfluoxetine hydrochloride by cytochrome P450 (CYP) 2D6, CYP2C19, and CYP3A4. Norfluoxetine hydrochloride inhibits 5-HT uptake and inhibits CaV3.3 T current (IC50 = 5 μM). Norfluoxetine hydrochloride has anticonvulsant activity[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

[Target]

5-HT Receptor

Cav3.3:5 μM (IC50)

[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].

[References]

[1]. Valéria Kecskeméti, et al. Norfluoxetine and fluoxetine have similar anticonvulsant and Ca2+ channel blocking potencies. Brain Res Bull. 2005 Sep 30;67(1-2):126-32.

[2]. Achraf Traboulsie, et al. T-type calcium channels are inhibited by fluoxetine and its metabolite norfluoxetine. Mol Pharmacol. 2006 Jun;69(6):1963-8.

[3]. Hyeon-Cheol Jeong, et al. Prediction of Fluoxetine and Norfluoxetine Pharmacokinetic Profiles Using Physiologically Based Pharmacokinetic Modeling. Clin Pharmacol. 2021 Nov;61(11):1505-1513.

[4]. D T Wong, et al. Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology. 1993 Jun;8(4):337-44.

Chemical & Physical Properties

[ Density]:
1.204g/cm3

[ Boiling Point ]:
381.1ºC at 760 mmHg

[ Molecular Formula ]:
C₁₆H₁₇ClF₃NO

[ Molecular Weight ]:
331.760

[ Flash Point ]:
184.3ºC

[ Exact Mass ]:
331.095062

[ PSA ]:
35.25000

[ LogP ]:
5.67660

[ Water Solubility ]:
H2O: >4 mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Articles

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TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel g...

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model.

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Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent t...

Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and N-desmethyldiltiazem.

Drug Metab. Dispos. 38(6) , 963-72, (2010)

Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hyd...