Description

Buy Fenfluramine (Fintepla) Cas 458-24-2

Fenfluramine, sold under the brand name Fintepla, is a serotonergic medication used for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome.^[2][6][3] It was formerly used as an appetite suppressant in the treatment of obesity, but was discontinued for this use due to cardiovascular toxicity before being repurposed for new indications.^[7][8] Fenfluramine was used for weight loss both alone under the brand name Pondimin and in combination with phentermine commonly known as fen-phen.^[7][9][10] Side effects of fenfluramine in people treated for seizures include decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, abnormal echocardiogram, fatigue, malaise, asthenia, ataxia, balance disorder, gait disturbance, increased blood pressure, drooling, excessive salivation, fever, upper respiratory tract infection, vomiting, appetite loss, weight loss, falls, and status epilepticus.^[2] Fenfluramine acts as a serotonin and norepinephrine releasing agent, agonist of the serotonin 5-HT₂ receptors, and sigma σ₁ receptor positive modulator.^[11][12][13] Its mechanism of action in the treatment of seizures is unknown,^[2] but may involve increased activation of certain serotonin receptors and the sigma σ₁ receptor.^[12][8][14] Chemically, fenfluramine is a phenethylamine and amphetamine.^[11] Fenfluramine was developed in the early 1960s and was first introduced for medical use as an appetite suppressant in France in 1963 followed by approval in the United States in 1973.^[7] In the 1990s, fenfluramine came to be associated with cardiovascular toxicity, and because of this, was withdrawn from the United States market in 1997.^[7][15] Subsequently, it was repurposed for the treatment of seizures and was reintroduced in the United States and the European Union in 2020.^[6][3][8] Fenfluramine was previously a schedule IV controlled substance in the United States.^[6] However, the substance has since no-longer been subject to control pursuant to rule-making issued on 23 December 2022.^[16] Fenfluramine is indicated for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome in people age two and older.^[2][6][3] Dravet syndrome is a life-threatening, rare and chronic form of epilepsy.^[6] It is often characterized by severe and unrelenting seizures despite medical treatment.^[6] Research is indicating a potential of fenfluramine to treat those with Sunflower syndrome, a rare form of epilepsy often manifesting in distinct hand waiving in front of the face and a tendency to stare at or face the sun.^[17] Fenfluramine was formerly used as an appetite suppressant in the treatment of obesity, but was withdrawn for this use due to cardiovascular toxicity.^[7] The most common adverse reactions in people with seizures include decreased appetite; drowsiness, sedation and lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue or lack of energy; ataxia (lack of coordination), balance disorder, gait disturbance (trouble with walking); increased blood pressure; drooling, salivary hypersecretion (saliva overproduction); pyrexia (fever); upper respiratory tract infection; vomiting; decreased weight; risk of falls; and status epilepticus.^[6] The U.S. Food and Drug Administration (FDA) fenfluramine labeling includes a boxed warning stating the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH).^[6] Because of the risks of VHD and PAH, fenfluramine is available only through a restricted drug distribution program, under a risk evaluation and mitigation strategy (REMS).^[6] The fenfluramine REMS requires health care professionals who prescribe fenfluramine and pharmacies that dispense fenfluramine to be specially certified in the fenfluramine REMS and that patients be enrolled in the REMS.^[6] As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring with echocardiograms to receive fenfluramine.^[6] At higher therapeutic doses, headache, diarrhea, dizziness, dry mouth, erectile dysfunction, anxiety, insomnia, irritability, lethargy, and CNS stimulation have been reported with fenfluramine.^[5] There have been reports associating chronic fenfluramine treatment with emotional instability, cognitive deficits, depression, psychosis, exacerbation of pre-existing psychosis (schizophrenia), and sleep disturbances.^[5][18] It has been suggested that some of these effects may be mediated by serotonergic neurotoxicity/depletion of serotonin with chronic administration or activation of serotonin 5-HT_2A receptors.^{[18][19][20][21]} The distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and chordae tendineae. One mechanism used to explain this phenomenon involves heart valve serotonin receptors, which are thought to help regulate growth. Since fenfluramine and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals.^[22] Fenfluramine and its active metabolite norfenfluramine affect the 5-HT_2B receptors, which are plentiful in human cardiac valves. The suggested mechanism by which fenfluramine causes damage is through over or inappropriate stimulation of these receptors leading to inappropriate valve cell division. Supporting this idea is the fact that this valve abnormality has also occurred in patients using other drugs that act on 5-HT_2B receptors.^[23][24] According to a study of 5,743 former users conducted by a plaintiff's expert cardiologist, damage to the heart valve continued long after stopping the medication.^[25] Of the users tested, 20% of women, and 12% of men were affected. For all ex-users, there was a 7-fold increase of chances of needing surgery for faulty heart valves caused by the drug.^[25]