(+)-Norfenfluramine is the major hepatic metabolite of (+)-fenfluramine and is a selective 5-HT2B receptor agonist (Ki: 11.2 nM). (+)-Norfenfluramine effectively stimulates the hydrolysis of phosphoinositide and increases intracellular Ca2+. (+)-Norfenfluramine may be utilized in the research of primary pulmonary hypertension and valvular heart disease.

Physicochemical Properties

Molecular Formula	C10H12F3N
Molecular Weight	203.20
Exact Mass	203.092
CAS #	19036-73-8
Related CAS #	(+)-Norfenfluramine hydrochloride;37936-89-3;Norfenfluramine;1886-26-6
PubChem CID	9815618
Appearance	Colorless to light yellow liquid
Density	1.152g/cm3
Boiling Point	215.2ºC at 760mmHg
Flash Point	88.9ºC
Vapour Pressure	0.15mmHg at 25°C
Index of Refraction	1.467
LogP	3.295
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	14
Complexity	179
Defined Atom Stereocenter Count	1
SMILES	FC(C1=CC=CC(=C1)C[C@H](C)N)(F)F
InChi Key	MLBHFBKZUPLWBD-ZETCQYMHSA-N
InChi Code	InChI=1S/C10H12F3N/c1-7(14)5-8-3-2-4-9(6-8)10(11,12)13/h2-4,6-7H,5,14H2,1H3/t7-/m0/s1
Chemical Name	(2S)-1-[3-(trifluoromethyl)phenyl]propan-2-amine
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	5-HT2B Receptor 11.2 nM (Ki) 5-HT2A Receptor 1516 nM (Ki) 5-HT2C Receptor 324 nM (Ki)
ln Vitro	In rats, arteries with a significant drop in threshold (the mesenteric resistance artery and the aorta) contract when exposed to (1 nM to 100 μM) with (+)-norfenfluramine[1]. Aortic contraction is induced in tissues of normotensive and hypertensive rats by (+)-Norfenfluramine (1 and 10 μM, 3 min)[1]. Rat hippocampus synaptosomes release 5-HT in a Ca2+-dependent manner when exposed to (0–10 μM)-Norfenfluramine for three minutes [2].
ln Vivo	In conscious SHAM and DOCA-salt rats, (+)-Norfenfluramine (1-300 μg/kg, iv) generates a pressor response[1]. Rat telencephalon and brainstem 5-HT and 5-HIAA levels are decreased by (+)-Norfenfluramine (2.5 and 5 mg/kg, ip)[3].
Animal Protocol	Animal/Disease Models: Conscious SHAM and DOCA-salt rats[1]. Doses: 1-300 μg/kg Route of Administration: intravenous (iv) injection (iv), given in a cumulative fashion at 6-min intervals. Experimental Results: Induced pressor response in conscious SHAM and DOCA-salt rats. (change in mean arterial blood pressure at 300 μg/kg, mm Hg, SHAM vehicle=36, SHAM ketanserin=7, DOCA=51, DOCA ketanserin=19).
ADME/Pharmacokinetics	Metabolism / Metabolites (s)-norfenfluramine has known human metabolites that include 2-(3-(Trifluoromethyl)phenyl)ethanamine.
References	[1]. The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. J Pharmacol Exp Ther. 2007 May;321(2):485-91. [2]. In vitro studies on the mechanism by which (+)-norfenfluramine induces serotonin and dopamine release from the vesicular storage pool. Naunyn Schmiedebergs Arch Pharmacol. 1998 Sep;358(3):323-7. [3]. Is receptor activation involved in the mechanism by which (+)-fenfluramine and (+)-norfenfluramine deplete 5-hydroxytryptamine in the rat brain? Br J Pharmacol. 1982 Mar;75(3):525-30.
Additional Infomation	(2S)-1-[3-(trifluoromethyl)phenyl]-2-propanamine is a member of amphetamines. A FENFLURAMINE analog that inhibits serotonin uptake and may provoke release of serotonin. It is used as an appetite depressant and an experimental tool in animal studies. See also: Norfenfluramine (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (492.13 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (12.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (12.30 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.9213 mL	24.6063 mL	49.2126 mL
	5 mM	0.9843 mL	4.9213 mL	9.8425 mL
	10 mM	0.4921 mL	2.4606 mL	4.9213 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.