Фенфлурамин

Side effects

In December 2012, the US Drug Enforcement Administration proposed classifying lorcaserin as a drug because it has hallucinogenic properties at higher than approved doses and users could develop psychiatric dependencies on the drug. On 7 May 2013, the US Drug Enforcement Administration classified lorcaserin as a Schedule IV drug under the Controlled Substances Act.

There has been concern that lorcaserin can cause cardiac valvulopathy based upon the reports of subjects taking the drug in Phase 2 trials. However, a Phase 3 clinical trial of the drug was conducted and the results published in the October 2014 Postgraduate Medicine journal, a peer-reviewed medical journal for physicians. These results found no statistically significant differences in valvulopathy rates compared to control, being 2.4% for the drug subjects and 2.0% for controls.

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE
Lorcaserin

DRUG CAS REGISTRY NUMBER MOLECULAR FORMULA STRUCTURE
Lorcaserin 616202-92-7 C11-H14-CI-N

ANNOTATED BIBLIOGRAPHY
Lorcaserin

References updated: 20 May 2019

  1. Chan EW, He Y, Chui CS, Wong AY, Lau WC, Wong IC. Efficacy and safety of
    lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled
    trials (RCTs) and narrative review on short-term RCTs. Obes Rev 2013; 14: 383-92. PubMed Citation  (Systematic review of results from 5 randomized controlled trials of lorcaserin, only 3 of which used the agent for more than 12 weeks; no mention of hepatotoxicity or ALT elevations).

  2. Nigro SC, Luon D, Baker WL. Lorcaserin: a novel serotonin 2C agonist for the treatment of obesity. Curr Med Res Opin 2013; 29: 839-48.
    PubMed Citation  (Review of the mechanism of action, efficacy and safety of lorcaserin as therapy of obesity; no mention of liver injury or ALT elevations). 

  3. Lorcaserin. In obesity: unacceptable risks. Prescrire Int 2014; 23: 117-20. PubMed Citation  (Review of the efficacy and safety of lorcaserin concludes that its weight loss effects are minimal and short-lived, and that its costs and risks of adverse events do not warrant its use as therapy of obesity).

  4. Halpern B, Halpern A. Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.
    Expert Opin Drug Saf 2015; 14: 305-15. PubMed Citation  (Review of the safety and efficacy of FDA approved medications for obesity including lorcaserin).

  5. Smith SR, Garvey WT, Greenway FL, Zhou S, Fain R, Pilson R, Fujioka K, et al. Coadministration of lorcaserin and phentermine for weight management: A
    12-week, randomized, pilot safety study. Obesity (Silver Spring) 2017; 25: 857-65. PubMed Citation  (Among 235 overweight or obese, non-diabetic adults treated with lorcaserin alone or wiht phentermine , weight loss was greater with the combination but so were side effects, but «there was no evidence of hepatic or renal toxicity»).

  6. Bohula EA, Scirica BM, Inzucchi SE, McGuire DK, Keech AC, Smith SR, Kanevsky E, et al; CAMELLIA-TIMI 61 Steering Committee Investigators.
    Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised,
    placebo-controlled trial. Lancet 2018; 392 (10161): 2269-79. PubMed Citation  (Among 12,000 overweight or obese adults treated with lorcaserin or placebo for a median of 3.3 years, weight loss was greater with lorcaserin by approximately 2.6 kg; no mention of ALT elevations or other adverse events).

  7. Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im K, Fanola CL, et al; CAMELLIA–TIMI 61 Steering Committee and Investigators.
    Cardiovascular safety of lorcaserin in overweight or obese patients. N Engl J Med 2018; 379: 1107-17. PubMed Citation  (Further analysis of trial of lorcaserin in 12,000 overweight or obese adults focusing upon safety and adverse events mentions adverse events «possible» to include dizziness, fatigue, headache, diarrhea and nausea; no mention of ALT elevations or hepatotoxicity).

  8. Tuccinardi D, Farr OM, Upadhyay J, Oussaada SM, Mathew H, Paschou SA, Perakakis N, et al. Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A
    six-month, randomized, placebo-controlled, double-blind clinical trial. Diabetes Obes Metab 2019; 21: 1487-92. PubMed Citation  (Among 48 obese adults treated with lorcaserin or placebo for 6 months, weight loss was greater with lorcaserin as were decreases in hepatic fat index, while ALT and AST levels were normal and remained normal with therapy).

OTHER REFERENCE LINKSLorcaserin

Pharmacology

Pharmacodynamics

Fenfluramine acts primarily as a serotonin releasing agent. It increases the level of serotonin, a neurotransmitter that regulates mood, appetite and other functions. Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter, and reversing serotonin transporter function. The drug also acts as a norepinephrine releasing agent to a lesser extent, particularly via its active metabolite norfenfluramine. At high concentrations, norfenfluramine, though not fenfluramine, also acts as a dopamine releasing agent, and so fenfluramine may do this at very high doses as well. In addition to monoamine release, while fenfluramine binds only very weakly to the serotonin 5-HT2 receptors, norfenfluramine binds to and activates the serotonin 5-HT2B and 5-HT2C receptors with high affinity and the serotonin 5-HT2A receptor with moderate affinity. The result of the increased serotonergic and noradrenergic neurotransmission is a feeling of fullness and reduced appetite.

The combination of fenfluramine with phentermine, a norepinephrine–dopamine releasing agent acting primarily on norepinephrine, results in a well-balanced serotonin–norepinephrine releasing agent with weaker effects of dopamine release.

Fenfluramine, phentermine, and monoamine release (EC50, nM)
Drug NE DA 5-HT Type Ref
Fenfluramine 739 >10,000 79.3–108 SRA
  D-Fenfluramine 302 >10,000 51.7 SNRA
  L-Fenfluramine >10,000 >10,000 147 SRA
Norfenfluramine 168–170 1,900–1,925 104 SNRA
Phentermine 39.4 262 3,511 NDRA

Pharmacokinetics

The elimination half-life of fenfluramine has been reported as ranging from 13 to 30 hours. The mean elimination half-lives of its enantiomers have been found to be 19 hours for dexfenfluramine and 25 hours for levfenfluramine. Norfenfluramine, the major active metabolite of fenfluramine, has an elimination half-life that is about 1.5 to 2 times as long as that of fenfluramine, with mean values of 34 hours for dexnorfenfluramine and 50 hours for levnorfenfluramine.

Эффективность препарата

Эффективность средства подтверждена клиническими исследованиями. Согласно испытаниям, препарат не причиняет такого вреда здоровью, как иные средства. В связи с этим производитель получил разрешение на реализацию продукта.

В исследовании приняли участие более 8000 человек. Люди были разделены на две группы. Однако часть принимала препарат, другая – простые витамины под видом средства для похудения. Совместно с употреблением продукта худеющим было предписано соблюдать диету и увеличить физическую нагрузку. В результате у группы, принимающий препарат, на 5% показатели были лучше.

В конце испытания были зафиксированы следующие результаты. 90% людей из группы, принимающей препарат, избавились от лишнего веса. Худеющие потеряли от 5,8 до 40% от первоначальной массы тела за 12 месяцев. Зафиксировано также, что у группы, принимающей препарат, стабилизировалось давление, и нормализовалась концентрация холестерина в крови.

Society and culture

Recreational use

Unlike various other amphetamine derivatives, fenfluramine is reported to be dysphoric, «unpleasantly lethargic», and non-addictive at therapeutic doses. However, it has been reported to be used recreationally at high doses ranging between 80 and 400 mg, which have been described as producing euphoria, amphetamine-like effects, sedation, and hallucinogenic effects, along with anxiety, nausea, diarrhea, and sometimes panic attacks, as well as depressive symptoms once the drug had worn off. At very high doses (e.g., 240 mg, or between 200–600 mg), fenfluramine induces a psychedelic state resembling that produced by lysergic acid diethylamide (LSD). Indirect (via induction of serotonin release) and/or direct activation of the 5-HT2A receptor would be expected to be responsible for the psychedelic effects of the drug at sufficient doses.

Spectra

Mass Spec (NIST)
Not Available
Spectra
Spectrum Spectrum Type Splash Key
Predicted MS/MS Spectrum — 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum — 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum — 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum — 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum — 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum — 40V, Negative (Annotated) Predicted LC-MS/MS Not Available

Identification

Name
Lorcaserin
Accession Number
DB04871
Type
Small Molecule
Groups
Approved
Description

Lorcaserin (previously APD-356), a highly selective 5HT2C receptor agonist, is used for the treatment of obesity. It has been shown to reduce body weight and food intake in animal models of obesity, and it is thought that targeting the 5HT2C receptor may alter body weight by regulating satiety. Lorcaserin is marketed as a salt form called Belviq, which is lorcaserin hydrochloride.

Structure
Synonyms
  • Lorcaserin
  • Lorqess
Product Ingredients
Ingredient UNII CAS InChI Key
Lorcaserin hydrochloride 0QJF08GDPE 846589-98-8 ITIHHRMYZPNGRC-QRPNPIFTSA-N
Lorcaserin hydrochloride hemihydrate REV26SR2B4 856681-05-5 WRZCAWKMTLRWPR-VSODYHHCSA-N
Prescription Products

Additional Data Available

  • Application Number

    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code

    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Lorqess
Categories
  • Alimentary Tract and Metabolism
  • Antidepressive Agents
  • Antiobesity Preparations, Excl. Diet Products
  • Central Nervous System Depressants
  • Centrally Acting Antiobesity Products
  • Cytochrome P-450 CYP1A2 Substrates
  • Cytochrome P-450 CYP2A6 Substrates
  • Cytochrome P-450 CYP2B6 Substrates
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Cytochrome P-450 CYP2D6 Inhibitors (moderate)
  • Cytochrome P-450 CYP2D6 Substrates
  • Cytochrome P-450 CYP3A Substrates
  • Cytochrome P-450 CYP3A4 Substrates
  • Cytochrome P-450 CYP3A4 Substrates (strength unknown)
  • Drugs that are Mainly Renally Excreted
  • Heterocyclic Compounds, Fused-Ring
  • Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
  • Serotonin 2c Receptor Agonists
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT2C Receptor Agonists
  • Serotonin Agents
  • Serotonin Modulators
  • Serotonin Receptor Agonists
UNII
637E494O0Z
CAS number
616202-92-7
Weight
Average: 195.69 Monoisotopic: 195.0814772
Chemical Formula
C11H14ClN
InChI Key
XTTZERNUQAFMOF-QMMMGPOBSA-N
InChI
InChI=1S/C11H14ClN/c1-8-7-13-5-4-9-2-3-10(12)6-11(8)9/h2-3,6,8,13H,4-5,7H2,1H3/t8-/m0/s1
IUPAC Name
(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
SMILES
C1CNCCC2=CC=C(Cl)C=C12

Лоркасерин побочные эффекты

Разработчик средства проводил испытания с целью выявить побочные эффекты. Их много, они страшные, но на кону твои минус 10 кг за неделю.

  • Тошнота, головокружение, слабость в ногах и сухость во рту;
  • Высокая температура с запорами;
  • Потеря памяти и зрения;
  • Повышенная потливость, озноб, воспаление миндалин;
  • Боль в мышцах, потеря слуха, кровь в моче;
  • Нервные припадки и бессонница.

Во время беременности

Всем беременным и кормящим женщинам подальше держаться от этого чудо средства. Даже те, кто планируют зачать ребенка должны отказаться от такого способа похудения. Вещество не прошло проверку местных специалистов из Америки на совместимость с беременностью.

В качестве побочных эффектов возможны задержки в развитии плода, развитие патологий и даже летальный исход. При лактации ферменты попадают в молоко, провоцируя множественные дисфункции у малышей.

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Form Route Strength
Tablet Oral 10 mg/1
Tablet, film coated, extended release Oral 20 mg/1
Prices
Not Available
Patents
Patent Number Pediatric Extension Approved Expires (estimated)
Unlock Additional Data
US6953787 No 2005-10-11 2023-04-10 US
US7514422 No 2009-04-07 2023-04-10 US
US7977329 No 2011-07-12 2023-04-10 US
US8207158 No 2012-06-26 2023-04-10 US
US8273734 No 2012-09-25 2023-04-10 US
US8546379 No 2013-10-01 2023-04-10 US
US8367657 No 2013-02-05 2023-04-10 US
US8575149 No 2013-11-05 2023-04-10 US
US9169213 No 2015-10-27 2032-12-06 US
US8999970 No 2015-04-07 2033-02-07 US
US8980881 No 2015-03-17 2025-12-20 US
US8946207 No 2015-02-03 2024-06-16 US
US8168624 No 2012-05-01 2029-04-18 US
US8697686 No 2014-04-15 2025-12-20 US
US7169401 No 2007-01-30 2023-07-18 US
US9770455 No 2017-09-26 2031-08-31 US
US10226471 No 2019-03-12 2031-08-31 US

Additional Data Available

Filed On

Filed On
The date on which a patent was filed with the relevant government.
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Стоимость

Купить в Москве или другом городе России средство не выйдет, даже если рецепт имеется. Синие таблеточки можно получить на территории США только по предписанию врача. Средство считается наркотическим, употребление и распространение отслеживается местными властями. К слову, оно содержит психотропные вещества.

Единственный возможный способ покупки – незаконный вывоз и ввоз на территорию твоей страны. Годовой курс препарата оценивается в 936 долларов, а цена в аптеках обычной упаковки – 78 долларов. Более того, проверить подлинность препарата практически невозможно, так как продавать тебе его будут вне закона.

Clinical Trials

Clinical Trials
Recruiting Treatment Cannabis Use Disorders
1 Completed Not Available BMI >30 kg/m2
1 Completed Basic Science Cocaine Use Disorders
1 Completed Diagnostic Cocaine Abuse
1 Completed Other BMI >30 kg/m2
1 Completed Other Healthy Participants
1 Completed Other Healthy Volunteers Substance Abuse
1 Completed Other Hepatic Impairment
1 Completed Other Impaired Renal Function
1 Completed Other Pharmacokinetics in Obese Adolescents
1 Completed Treatment BMI >30 kg/m2
1 Completed Treatment Cannabis Use Disorders
1 Completed Treatment Healthy Volunteers
1 Completed Treatment Opioid Abuse Opioid Dependence Opioid-Related Disorders Opioids Use
1 Enrolling by Invitation Prevention Cardiovascular Disease (CVD)
1 Recruiting Basic Science Dependence, Cocaine
1 Recruiting Treatment Cocaine-Related Disorders Opioid-Related Disorders
1, 2 Active Not Recruiting Basic Science Cannabis Use
1, 2 Completed Treatment Tobacco Use Disorders Weight gain therapy
1, 2 Enrolling by Invitation Treatment Muscle Weakness Sepsis
1, 2 Recruiting Treatment Cocaine Use Disorders
2 Active Not Recruiting Treatment Cocaine-Related Disorders
2 Completed Treatment BMI >30 kg/m2
2 Completed Treatment Cessation, Smoking
2 Completed Treatment Nicotine Dependence
2 Not Yet Recruiting Treatment Chemotherapy-induced Peripheral Neuropathy (CIPN)
2 Recruiting Treatment Cocaine Use Disorders
2, 3 Recruiting Treatment BMI >30 kg/m2 Cessation, Smoking
2, 3 Recruiting Treatment Opioid-use Disorder
3 Completed Treatment BMI >27 kg/m2 Obese
3 Completed Treatment BMI >30 kg/m2
3 Not Yet Recruiting Treatment BMI >30 kg/m2
4 Active Not Recruiting Treatment BMI >30 kg/m2 Obese experiencing rapid weight loss
4 Completed Treatment BMI >27 kg/m2 BMI >30 kg/m2 Cardiovascular Disease (CVD) High Cardiovascular Risk Type 2 Diabetes Mellitus
4 Completed Treatment Chronic Weight Management
4 Recruiting Other Overweight and Obesity
4 Recruiting Treatment BMI >27 kg/m2 Schizoaffective Disorders Schizophrenic Disorders
4 Recruiting Treatment BMI >30 kg/m2
4 Unknown Status Treatment Weight gain therapy
Not Available Active Not Recruiting Not Available BMI >27 kg/m2 BMI >30 kg/m2 Obese experiencing rapid weight loss
Not Available Completed Treatment BMI >30 kg/m2

Сведения к размышлению

Целых 14 лет средство не могло получить лицензии на распространение. Почему? Оно не соответствовало нормам здравоохранения. Хотя производитель подчеркивает высокую безопасность препарата, побочные эффекты говорят сами за себя.

В результате численных испытаний эффективность лоркасерина составила 5% в сравнении с контрольной группой, которая занималась спортом и здоровым питанием. Производитель позиционирует вещество, как пищевую добавку, хотя по своей сути это лекарство. Именно из-за того его распространение на территории РФ запрещено.

Мнения врачей

По составу препарат приближен к распространенным средствам родом из Франции, которые запрещены во всем мире. Все потому, что в его составе содержится субитрамин, который можно обнаружить во многих антидепрессантах. Они не только вызывают зависимость, но и повышают давление, нарушения кожного покрова, головные боли. Более того, в силу невозможности проверить подлинность средства, приобретение подобного средства может закончиться летальным исходом для покупателя.

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug Interaction
Unlock Additional Data
(R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Lorcaserin.
(S)-Warfarin The risk or severity of adverse effects can be increased when Lorcaserin is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamine The risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Lorcaserin.
2,5-Dimethoxy-4-ethylthioamphetamine The risk or severity of adverse effects can be increased when Lorcaserin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lorcaserin.
4-Bromo-2,5-dimethoxyamphetamine The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Lorcaserin.
4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Lorcaserin.
4-Methoxyamphetamine The metabolism of 4-Methoxyamphetamine can be decreased when combined with Lorcaserin.
5-androstenedione The metabolism of Lorcaserin can be decreased when combined with 5-androstenedione.
5-methoxy-N,N-dimethyltryptamine The risk or severity of adverse effects can be increased when Lorcaserin is combined with 5-methoxy-N,N-dimethyltryptamine.

Additional Data Available

  • Extended Description

    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity

    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level

    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action

    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

History

Fenfluramine was developed in the early 1960s and was introduced in France in 1963. Approximately 50 million Europeans were treated with fenfluramine for appetite suppression between 1963 and 1996. Fenfluramine was approved in the United States in 1973. The combination of fenfluramine and phentermine was proposed in 1984. Approximately 5 million people in the United States were given fenfluramine or dexfenfluramine with or without phentermine between 1996 and 1998.

In the early 1990s, French researchers reported an association of fenfluramine with primary pulmonary hypertension and dyspnea in a small sample of patients. Fenfluramine was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. It was banned in India in 1998.

Adverse effects

At higher therapeutic doses, headache, diarrhea, dizziness, dry mouth, erectile dysfunction, anxiety, insomnia, irritability, lethargy, and CNS stimulation have been reported with fenfluramine.

There have been reports associating chronic fenfluramine treatment with emotional instability, cognitive deficits, depression, psychosis, exacerbation of pre-existing psychosis (schizophrenia), and sleep disturbances. It has been suggested that some of these effects may be mediated by serotonergic neurotoxicity/depletion of serotonin with chronic administration and/or activation of serotonin 5-HT2A receptors.

Heart valve disease

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. Fenfluramine and its active metabolite norfenfluramine affect the 5-HT2B 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-HT2B receptors.

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. 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.

Properties

State
Solid
Experimental Properties
Property Value Source
water solubility Water solubility is greater than 400 mg/mL. From FDA label.
Predicted Properties
Property Value Source
Water Solubility 0.0709 mg/mL ALOGPS
logP 3 ALOGPS
logP 2.83
logS -3.4 ALOGPS
pKa (Strongest Basic) 10.12
Physiological Charge 1
Hydrogen Acceptor Count 1
Hydrogen Donor Count 1
Polar Surface Area 12.03 Å2
Rotatable Bond Count
Refractivity 56.65 m3·mol-1
Polarizability 21.51 Å3
Number of Rings 2
Bioavailability 1
Rule of Five Yes
Ghose Filter Yes
Veber’s Rule Yes
MDDR-like Rule No
Predicted ADMET features
Not Available

Mechanism of action

Lorcaserin is a selective 5-HT2C receptor agonist, and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets. 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus. The activation of 5-HT2C receptors in the hypothalamus is supposed to activate proopiomelanocortin (POMC) production and consequently promote weight loss through satiety. This hypothesis is supported by clinical trials and other studies. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, and endocrine secretion, the exact mechanism of appetite regulation is not yet known. Lorcaserin has shown 100x selectivity for 5-HT2C versus the closely related 5-HT2B receptor, and 17x selectivity over the 5-HT2A receptor.

Receptor EC50 Ki
5-HT2C 39 13
5-HT2B 2380 147
5-HT2A 553 92

LORCASERIN

OVERVIEW
Lorcaserin

Lorcaserin (lor ka’ ser in) is a serotonin agonist that is relatively selective for the serotonin 2C (5-HT2C) receptor, that is located almost exclusively in the brain.  Activation of this receptor activates pathways important in hunger and satiety, including those that induce proopiomelanocortin which decreases appetite.  In several premarketing controlled trials, lorcaserin was found to lead to greater weight loss than placebo.  Lorcaserin was officially approved for use in the United States in 2012, but was recommended only for patients who are obese (BMI
≥30) or who are overweight (BMI
≥27-30) and have a significant obesity related condition.  Lorcaserin is available in 10 mg tablets under the commercial name Belviq.  The recommended dose is 10 mg twice daily.  An extended release formulation, available as 20 mg tablets (Belviq XR), has been developed which is administered once daily.  Commonly reported side effects are headache, dry mouth, nausea, fatigue and dizziness which rarely require discontinuation or dose adjustment.  Severe side effects are rare and possibly included depression, serotonin syndrome and cardiac valvulopathy, although side effects were not appreciably increased among lorcaserin treated patients in pre-licensure clinical trials.

REPRESENTATIVE TRADE NAMES
Lorcaserin
– Belviq

DRUG CLASS
Weight Loss Agents

References

Synthesis Reference

Jandacek RJ: APD-356 (Arena). Curr Opin Investig Drugs. 2005 Oct;6(10):1051-6.

General References
  1. Halford JC: Obesity drugs in clinical development. Curr Opin Investig Drugs. 2006 Apr;7(4):312-8.
  2. Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Dosa PI, Covel JA, Ren A, Webb RR, Beeley NR, Martin M, Morgan M, Espitia S, Saldana HR, Bjenning C, Whelan KT, Grottick AJ, Menzaghi F, Thomsen WJ: Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J Med Chem. 2008 Jan 24;51(2):305-13. Epub 2007 Dec 21.
External Links
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Wikipedia
Lorcaserin
ATC Codes
A08AA11 — Lorcaserin
  • A08AA — Centrally acting antiobesity products
  • A08A — ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
  • A08 — ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
  • A — ALIMENTARY TRACT AND METABOLISM
FDA label
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Approval history

On 22 December 2009 a New Drug Application (NDA) was submitted to the Food and Drug Administration (FDA) in the United States. On 16 September 2010, an FDA advisory panel voted 9-5 against approval of the drug based on concerns over both efficacy and safety, particularly the findings of tumors in rats. On 23 October 2010, the FDA decided not to approve the drug based on the available data. This was not only because cancer promoting properties could not be ruled out, but also because the weight loss efficacy was considered «marginal.»

After additional studies were completed and additional information submitted to the FDA, an advisory panel was convened on 10 May 2012. The advisory panel voted 19-4-1 to recommend lorcaserin to the FDA. The FDA stated that the weight loss data passed FDA standards for efficacy and that the drug did not have cancer risks based on clarifications in the data. The FDA panelist recommended that postmarketing studies regarding potential heart valve issues be completed. On 27 June 2012, the FDA officially approved lorcaserin for use in the treatment of obesity for some adults.

On 10 May 2012, after a new round of studies submitted by Arena, an FDA panel voted to recommend lorcaserin with certain restrictions and patient monitoring. The restrictions include patients with a BMI of over 30, or with a BMI over 27 and a comorbidity such as high blood pressure or type 2 diabetes. On 27 June 2012, the FDA officially approved lorcaserin for use in the treatment of obesity for adults with a BMI equal to or greater than 30 or adults with a BMI of 27 or greater who «have at least one weight-related health condition, such as high blood pressure, type 2 diabetes, or high cholesterol.»

Итоги

Хотелось бы, чтобы одна таблетка решала все проблемы, однако правильное питание невозможно заменить фармацевтическими препаратами. Это не приведет к желаемому похудению, а лишь усугубит существующую проблему. Что тебя ждет после принятия таблеток:

  • Физическое и моральное истощение. Представим, что активные вещества действительно блокируют участки мозга, которые отвечают за голод (бред конечно), но твой организм продолжает требовать необходимые макро и микроэлементы. Уже через несколько дней чрезмерной активности твое состояние ухудшится, это приведет к нервным срывам и потери сна. Это все негативно влияет на процесс сжигания подкожного жира.
  • Процесс обмена веществ нарушится. Подобный стресс только мешает твоему метаболизму. В процессе употребления препарата есть риск набрать небольшой вес. Ну а если чудом тебе удастся сбросить хоть 5% от общей массы, то дополнительные 10% станут неприятным бонусом по окончанию курса.
  • Твой иммунитет ослабнет. Подобное состояние организма ведет к ухудшению его защитных функций. Это прекрасная почва для развития или проявления давно забытых патологий.

В отзывах действительно можно расхвалить купленное за рубежом средство. Однако пользы от его покупки ты не получишь. И если тебя не пугают многочисленные побочные эффекты от таблеток, следует подумать, что потраченные деньги просто уйдут на ветер.

Список источников

  • dieta4y.ru
  • SmotriVita.ru
  • www.drugbank.ca
  • wiki2.org
  • livertox.nih.gov
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