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

Physicochemical Properties

Molecular Formula	C10H13CLF3N
Molecular Weight	239.67
Exact Mass	239.069
CAS #	37936-89-3
Related CAS #	(+)-Norfenfluramine;19036-73-8
PubChem CID	71311600
Appearance	White to off-white solid powder
LogP	4.097
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	15
Complexity	179
Defined Atom Stereocenter Count	1
SMILES	C[C@@H](CC1=CC(=CC=C1)C(F)(F)F)N.Cl
InChi Key	PIDLOFBRTWNFAR-FJXQXJEOSA-N
InChi Code	InChI=1S/C10H12F3N.ClH/c1-7(14)5-8-3-2-4-9(6-8)10(11,12)13;/h2-4,6-7H,5,14H2,1H3;1H/t7-;/m0./s1
Chemical Name	(2S)-1-[3-(trifluoromethyl)phenyl]propan-2-amine;hydrochloride
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: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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-HT2C Receptor 324 nM (Ki) 5-HT2A Receptor 1516 nM (Ki)
ln Vitro	Rats' aorta and mesenteric resistance arteries, which have a sharply decreased threshold, are contracted by (+)-norfenfluramine hydrochloride (1 nM to 100 μM)[1]. Rat tissues with normotensive and hypertension conditions exhibit aortic contraction in response to (+)-norfenfluramine hydrochloride (1 and 10 μM, 3 min)[1]. 5-HT release from rat hippocampus synaptosomes is induced by (+)-Norfenfluramine (0-10 μM, 3 min) hydrochloride in a Ca2+-dependent manner [2].
ln Vivo	In conscious SHAM and DOCA-salt rats, (+)-Norfenfluramine (1-300 μg/kg, iv) hydrochloride causes a pressor response[1]. Rat telencephalon and brainstem 5-HT and 5-HIAA levels are decreased by (+)-Norfenfluramine hydrochloride (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).
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.

Solubility Data

Solubility (In Vitro)

H2O: 18.75 mg/mL (78.23 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.1724 mL	20.8620 mL	41.7240 mL
	5 mM	0.8345 mL	4.1724 mL	8.3448 mL
	10 mM	0.4172 mL	2.0862 mL	4.1724 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.