(+)-Norfenfluramine

Names

[ CAS No. ]:
19036-73-8

[ Name ]:
(+)-Norfenfluramine

[Synonym ]:
dexnorfenfluramine
Dexibuprofen Lysine
d-norfenfluramine

Biological Activity

[Description]:

(+)-Norfenfluramine a major hepatic metabolite of (+)-fenfluramine, is a selective 5-HT2B receptor agonist (Ki: 11.2 nM). (+)-Norfenfluramine potently stimulates the hydrolysis of inositol phosphates and increases intracellular Ca2+. (+)-Norfenfluramine can be used for the research of primary pulmonary hypertension and valvular heart disease[1].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

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

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

[Target]

5-HT2B Receptor:11.2 nM (Ki)

5-HT2A Receptor:1516 nM (Ki)

5-HT2C Receptor:324 nM (Ki)

[In Vitro]

(+)-Norfenfluramine (1 nM to 100 μM) contracts arteries with a dramatic decrease in threshold (aorta and mesenteric resistance artery) in rats[1]. (+)-Norfenfluramine (1 and 10 μM, 3 min) induces contraction in aorta from tissues of normotensive and hypertensive rats[1]. (+)-Norfenfluramine (0-10 μM, 3 min) induces 5-HT release from rat hippocampal synaptosomes by Ca2+-dependent way [2].

[In Vivo]

(+)-Norfenfluramine (1-300 μg/kg, i.v.) induces pressor response in conscious SHAM and DOCA-salt rats[1]. (+)-Norfenfluramine (2.5 and 5 mg/kg, i.p.) decreases of 5-HT and 5-HIAA levels in telencephalon and brainstem of rats[3]. Animal Model: Conscious SHAM and DOCA-salt rats[1]. Dosage: 1-300 μg/kg Administration: Intravenous injection (i.v.), given in a cumulative fashion at 6-min intervals. Result: 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]. Wei Ni, et al. 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]. M Gobbi, et al. 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]. R Invernizzi, et al. 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.

Chemical & Physical Properties

[ Density]:
1.152g/cm3

[ Boiling Point ]:
215.2ºC at 760mmHg

[ Molecular Formula ]:
C₁₀H₁₂F₃N

[ Molecular Weight ]:
203.20400

[ Flash Point ]:
88.9ºC

[ Exact Mass ]:
203.09200

[ PSA ]:
26.02000

[ LogP ]:
3.29540

[ Vapour Pressure ]:
0.15mmHg at 25°C

[ Index of Refraction ]:
1.467

Safety Information

[ HS Code ]:
2921499090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2921499090

[ Summary ]:
2921499090 other aromatic monoamines and their derivatives; salts thereof VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%