Fenfluramine

Structural formula
	( R ) shape (top) and ( S ) shape (bottom)
General
Non-proprietary name	Fenfluramine
other names	( RS ) - N -ethyl-1- [3- (trifluoromethyl) phenyl] propan-2-amine
Molecular formula	C 12 H 16 F 3 N (fenfluramine) ; C 12 H 16 F 3 N HCl (fenfluramine hydrochloride) ;
External identifiers / databases
ECHA InfoCard	100.006.616
PubChem	3337
DrugBank	DB00574
Wikidata	Q418928
Drug information
ATC code	A08 AA02 , A08 AA04
Drug class	Anorectics
properties
Molar mass	231.26 g · mol -1 (fenfluramine) ; 267.72 g · mol -1 (· fenfluramine hydrochloride) ;
Melting point	166 ° C [( RS ) -fenfluramine hydrochloride] ; 160–161 ° C [( S ) -fenfluramine hydrochloride] ; 160–161 ° C [( R ) -fenfluramine hydrochloride] ;
boiling point	108–112 ° C (15.6 h Pa )
pK s value	4.9
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances danger
H and P phrases	H: 301
	P: 301 + 310
Toxicological data	144 mg kg −1 ( LD 50 , rat , oral , ( RS ) -fenfluramine) ; 114.5 mg kg −1 ( LD 50 , rat , oral , ( S ) -fenfluramine hydrochloride) ; 195 mg kg −1 ( LD 50 , rat , oral , ( R ) -fenfluramine hydrochloride) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fenfluramine is an anorectic (appetite suppressant) that is structurally related to amphetamine , but has no psycho-stimulating side effects. Rather, it has a slightly sedating effect and promotes drowsiness . The amine hydrochloride is used in preparations .

pharmacology

Dexfenfluramine or its main active metabolite N -norfenfluramin acts as a serotonin releaser and thus increases the (extracellular) serotonin level. It works next to the 5-HT _2C - agonist . Both serve the therapeutic purpose. Its (agonistic) action on 5-HT _2B receptors, which z. B. can also be found in the heart .

With regard to epilepsy (in Belgium the drug is still available by royal decree), positive experiences with therapy-refractory self-induced seizures with photosensitivity or other epilepsy as well as the triggering of acute symptomatic seizures have been reported.

Admission

The eutomer dextro-fenfluramine , dexfenfluramine for short ( Redux ) was manufactured by Interneuron Pharmaceuticals and sold by Wyeth-Ayerst Laboratories . During the 1990s, it was FDA approved for a number of years for the purpose of weight loss .

In 1997, fenfluramine / dexfenfluramine were withdrawn from circulation because of cardiac valve damage and pulmonary hypertension observed after long-term use . It is known from animal experiments that prolonged administration runs the risk of damaging the serotonin neurons in the brain.

Cardiac side effects may be reasonably low at the low doses used in epilepsy therapy. It is currently not foreseeable whether a readmission for epilepsy will take place.

Web links

Pharmaceutical information: Dexfenfluramine

Individual evidence

↑ ^a ^b ^c ^d ^e ^f The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 679.
↑ ^a ^b ^c Entry on fenfluramine. In: Römpp Online . Georg Thieme Verlag, accessed on July 1, 2019.
↑ ^a ^b data sheet (±) -Fenfluramine hydrochloride from Sigma-Aldrich , accessed on March 31, 2011 ( PDF ).
↑ V. Setola, M. Dukat, RA Glennon, BL Roth: Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor. In: Mol Pharmacol . 68 (1), Jul 2005, pp. 20-33. PMID 15831837 . Full text .
↑ J. Aicardi, H. Gastaut: Treatment of self-induced photosensitive epilepsy with fenfluramine (letter). In: N Engl J Med. 313, 1985, p. 1419.
↑ M. Boel, P. Casaer: Add-on therapy of fenfluramine in intractable self-induced epilepsy. In: Neuropediatrics. 27, 1996, pp. 171-173.
↑ H. Gastaut, BG Zifkin: Anti-epileptic effects of fenfluramine: pilot study (abstract). In: Ann Neurol. 22, 1987, pp. 414-415.
↑ B. Ceulemans, M. Boel, K. Leyssens et al .: Successful use of fenfluramine as an add-on treatment for Dravet syndrome. In: Epilepsia. 53, 2012, pp. 1131-1139.
↑ B. Ceulemans, AS Schoonjans, F. Marchau et al .: Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine. In: Epilepsia. 57, 2016, pp. E129 – e134.
↑ A. Schoonjans, BP Paelinck, F. Marchau et al .: Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients. In: Eur J Neurol. 24, 2017, pp. 309-314.
↑ DC Spencer, J. Hwang, MJ Morrell: Fenfluramine-phentermine (Fen-Phen) and seizures: Evidence for an association. In: Epilepsy Behav. 1, 2000, pp. 448-452.
↑ MA Khan, CA Herzog, JV St. Peter, GG Hartley, R. Madlon-Kay, CD Dick, RW Asinger, JT Vessey: The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs . In: N Engl J Med . tape 339 , no. 11 , 1998, pp. 713-718 ( full text . PMID 9731086 ).
^ Klaus Koch: New studies published: Appetite suppressants and heart damage. In: Dtsch Arztebl. 95 (41), 1998, pp. A-2496 / B-2150 / C-1997.
↑ Commentary on Dexfenfluramine . In: Pharmainformation. 8, No. 2, 1993, Retrieved August 11, 2009.
↑ AS Schoonjans, F. Marchau, BP Paelinck et al .: Cardiovascular safety of low-dose fenfluramine in Dravet syndrome: a review of its benefit-risk profile in a new patient population. In: Curr Med Res Opin. 33, 2017, pp. 1773–1781.

[MerckIndex-1] ↑ ^a ^b ^c ^d ^e ^f The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition. 2006, ISBN 0-911910-00-X , p. 679.

[roempp-2] Entry on fenfluramine. In: Römpp Online . Georg Thieme Verlag, accessed on July 1, 2019.

[Sigma-3] ta sheet (±) -Fenfluramine hydrochloride from Sigma-Aldrich , accessed on March 31, 2011 ( PDF ).

[4] V. Setola, M. Dukat, RA Glennon, BL Roth: Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor. In: Mol Pharmacol . 68 (1), Jul 2005, pp. 20-33. PMID 15831837 . Full text .

[5] J. Aicardi, H. Gastaut: Treatment of self-induced photosensitive epilepsy with fenfluramine (letter). In: N Engl J Med. 313, 1985, p. 1419.

[6] M. Boel, P. Casaer: Add-on therapy of fenfluramine in intractable self-induced epilepsy. In: Neuropediatrics. 27, 1996, pp. 171-173.

[7] H. Gastaut, BG Zifkin: Anti-epileptic effects of fenfluramine: pilot study (abstract). In: Ann Neurol. 22, 1987, pp. 414-415.

[8] B. Ceulemans, M. Boel, K. Leyssens et al .: Successful use of fenfluramine as an add-on treatment for Dravet syndrome. In: Epilepsia. 53, 2012, pp. 1131-1139.

[9] B. Ceulemans, AS Schoonjans, F. Marchau et al .: Five-year extended follow-up status of 10 patients with Dravet syndrome treated with fenfluramine. In: Epilepsia. 57, 2016, pp. E129 – e134.

[10] A. Schoonjans, BP Paelinck, F. Marchau et al .: Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients. In: Eur J Neurol. 24, 2017, pp. 309-314.

[11] DC Spencer, J. Hwang, MJ Morrell: Fenfluramine-phentermine (Fen-Phen) and seizures: Evidence for an association. In: Epilepsy Behav. 1, 2000, pp. 448-452.

[12] MA Khan, CA Herzog, JV St. Peter, GG Hartley, R. Madlon-Kay, CD Dick, RW Asinger, JT Vessey: The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs . In: N Engl J Med . tape 339 , no. 11 , 1998, pp. 713-718 ( full text . PMID 9731086 ).

[13] Klaus Koch: New studies published: Appetite suppressants and heart damage. In: Dtsch Arztebl. 95 (41), 1998, pp. A-2496 / B-2150 / C-1997.

[14] Commentary on Dexfenfluramine . In: Pharmainformation. 8, No. 2, 1993, Retrieved August 11, 2009.

[15] AS Schoonjans, F. Marchau, BP Paelinck et al .: Cardiovascular safety of low-dose fenfluramine in Dravet syndrome: a review of its benefit-risk profile in a new patient population. In: Curr Med Res Opin. 33, 2017, pp. 1773–1781.