(+)-Norfenfluramine hydrochloride

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

Research Areas >> Cardiovascular Disease

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

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

5-HT2B Receptor:11.2 nM (Ki)

5-HT2C Receptor:324 nM (Ki)

5-HT2A Receptor:1516 nM (Ki)

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

(+)-Norfenfluramine (1-300 μg/kg, i.v.) hydrochloride induces pressor response in conscious SHAM and DOCA-salt rats[1]. (+)-Norfenfluramine (2.5 and 5 mg/kg, i.p.) hydrochloride 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).

[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.