Lorcaserin

Lorcaserin

Systematic (IUPAC) name
(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
Clinical data
Trade names	Belviq
AHFS/Drugs.com	monograph
MedlinePlus	a613014
Licence data	US FDA:link
Pregnancy category	US: X (Contraindicated)
Legal status	US: Schedule IV
Routes of administration	Oral
Pharmacokinetic data
Protein binding	70%
Metabolism	Hepatic (extensive)
Biological half-life	11 hours
Excretion	Renal (92.3%), Faecal (2.2%)
Identifiers
CAS Number	616202-92-7 Y
ATC code	A08AA11 (WHO)
PubChem	CID: 11658860
IUPHAR/BPS	2941
ChemSpider	9833595 Y
UNII	637E494O0Z Y
ChEMBL	CHEMBL360328 Y
Synonyms	APD-356
Chemical data
Formula	C11H14ClN
Molecular mass	195.688 g/mol
SMILES Clc1cc2c(cc1)CCNC[C@@H]2C
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 Y Key:XTTZERNUQAFMOF-QMMMGPOBSA-N Y
NY (what is this?)  (verify)

Lorcaserin, currently marketed under the trade name Belviq and previously Lorqess during development, is a weight-loss drug developed by Arena Pharmaceuticals. It has serotonergic properties and acts as an anorectic.

Medical uses

Lorcaserin is used long term for weight loss in those who are obese.

Side effects

In clinical trials, the most common side effect was headache, experienced by about 18% of drug arm participants compared to 11% of placebo participants. Headache was the only reported side effect to occur at a frequency greater than 5 percentage points above those from placebo. Other reported side effects and their rates for lorcaserin and placebo patients, respectively, were as follows: upper respiratory tract infection (14.8% vs. 11.9%), nasopharyngitis (13.4% vs. 12.0%), sinusitis (7.2% vs. 8.2%), and nausea (7.5% vs. 5.4%). Adverse events of depression, anxiety, and suicidal ideation were infrequent and were reported at a similar rate in each treatment group.

On 15 September 2010 it was reported by national news media that lorcaserin was associated with the development of cancer in laboratory rats.

In December 2012, the US Drug Enforcement Administration proposed classifying lorcaserin as a Schedule IV 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 2.3% for the drug subjects and 2.2% for controls.

Mechanism of action

Lorcaserin is a selective 5-HT_2C receptor agonist, and in vitro testing of the drug showed reasonable selectivity for 5-HT_2C over other related targets. 5-HT_2C 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-HT_2C 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-HT_2C 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-HT_2C versus the closely related 5-HT_2B receptor, and 17x selectivity over the 5-HT_2A receptor.

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

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 to recommend against approval of the drug based on concerns over both safety and efficacy. In October 2010, the FDA stated that it could not approve the application for lorcaserin in its present form.

Lorcaserin had a Prescription Drug User Fee Act (PDUFA) date of 22 October 2010. On 16 September 2010, a federal advisory committee voted against recommending approval for lorcaserin. In their 9-5 vote, the committee raised concerns about the safety of the drug, 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. The FDA has not stated one way or the other whether they believe this is necessary at this time although no related safety markers have been indicated during clinical studies. 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."

See also

• Vabicaserin

External links

• Belviq Homepage

• Belviq Patient & Doctor Reviews