Identification
- Generic Name
- Fenproporex
- DrugBank Accession Number
- DB01550
- Background
Fenproporex is an orally active stimulant drug, which was developed in the 1960s. It is used as an appetite suppressant and a treatment for obesity. It is listed as an illicit substance in many countries due to addiction issues and listed as a prohibited substance by the World Anti-Doping Agency. Structurally, fenproporex (N-2-cyanoethylamphetamine) falls within the phenylethamine and amphetamine chemical class of drugs. The N-2-cyanoethyl substituent was once believed to be resistant to cleavage, because fenproporex -- once recommended as an obesity treatment for patients with cardiovascular disease -- was originally claimed to lack stimulant properties. Contrary to the claim, research has demonstrated easy in vivo cleavage of the N-2-cyanothyl substituent to yield amphetamine as a metabolite. [5] However, in clinical practice, central nervous system stimulative effects are less notorious than with some other agents such as diethylpropion and mazindol. [7]
In the United States fenproporex was never approved by the FDA for clinical use due to a lack of efficacy and safety data, and is listed as a drug in Schedule IV of the Controlled Substances Act. In 2006 and 2009, the FDA issued warnings that it had been detected in diet pills sold online, and imported from foreign manufacturers.
Despite being banned in the United States, fenproporex has been described as the second most commonly consumed appetite suppressant worldwide, [6] with fenproporex containing anorectics still being commonly prescribed in South America. Little is known about the specific hazards of amphetamine based diet pills, however case reports have noted side effects such as chest pain, palpitations, headaches, and insomnia. In addition, placebo controlled studies have shown that participants using fenproporex experience more joint pain, sweating, blurred vision and tremor. [2]
- Type
- Small Molecule
- Groups
- Experimental, Illicit, Withdrawn
- Structure
Structure for Fenproporex (DB01550)
- Weight
- Average: 188.2688
Monoisotopic: 188.131348522 - Chemical Formula
- C12H16N2
- Synonyms
- Femproporex
- Fenproporex
- Fenproporexum
Pharmacology
- Indication
Fenproporex is used as an appetite suppressant, and anti-obesity agent [2]; however, due to substance abuse potential, it is an illicit substance in many countries. In some countries, such as Brazil, it is still prescribed -- often in the form of diet pills (ie. Brazilian Diet Pills) which combine amphetamines, benzodiazepines, antidepressants, diuretics and laxatives.
In the United States the sale of such diet pills has been banned due to concerns over side effects, and the risk of potentially fatal overdose. However, internet sales and illicit markets has lead to international availability. It has been found by primary care physicians that Brazilian immigrant women utilized imported diet pills at particularly high rates, and sometimes suffered from side effects requiring hospitalization or experienced a loss of employment. [3]
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Fenproporex was first claimed to not exert a stimulant effect on the body, however research into its metabolism has shown that it is converted into a considerable amount of amphetamine in the body, which leads to stimulant effects. [9]
- Mechanism of action
Fenproporex is an amphetamine based anorectic which is rapidly metabolized into amphetamine in the body. Both acute and chronic fenproporex administration has been shown to increase brain energy metabolism in young rats, by increasing the activity of citrate synthase, malate dehydrogenase, succinate dehydrogenase, creatine kinase and complexes I,II, III, and IV. [8]
Amphetamine based drugs are also known to reduce food intake. They are addictive substances due to their ability to increase dopamine release, however their anorectic effects are believed to be a result of noradrenergic neurotransmission. Activation of the alpha 1 and beta 2 adrenoceptors has been shown to decrease food intake, and drugs which release norepinephrine or block norepinephrine reuptake can activate these receptors. [3]
The alpha 1 and beta 2 adrenoceptors are noted to be clinically important receptors in weight regulation. [3]
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
A large portion, 60-80%, of fenproporex is rapidly converted into amphetamine. Besides amphetamine, and unchanged fenproporex, 14 other metabolites were identified from urine samples.
Two interacting metabolic pathways are believed to exist. The major pathway is believed to involve ring-degradation by aromatic hydroxylation, methylation, and side chain degradation by N-dealkyation to form amphetamine. The minor pathway involves the beta-hydroxylation of amphetamine to form norephedrine. [6]
- Route of elimination
Renally eliminated in the urine, mainly as amphetamine, but 5-9% as unchanged drug.
- Half-life
Not Available
- Clearance
The amphetamine metabolite can be detected for several days after the administration of forproporex (up to 119h, in one study). [2]
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
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 Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Fenproporex which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Fenproporex which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Fenproporex which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Fenproporex which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Fenproporex which could result in a lower serum level and potentially a reduction in efficacy. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Desobesi-M (Aché) / Feprorex (Medix) / Lipenan (Sanofi-Aventis) / Salcal (Saval)
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenethylamines
- Direct Parent
- Amphetamines and derivatives
- Alternative Parents
- Phenylpropanes / Aralkylamines / Nitriles / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Amine / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound / Carbonitrile / Hydrocarbon derivative / Nitrile / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- W0194S5FOA
- CAS number
- 16397-28-7
- InChI Key
- IQUFSXIQAFPIMR-UHFFFAOYSA-N
- InChI
- InChI=1S/C12H16N2/c1-11(14-9-5-8-13)10-12-6-3-2-4-7-12/h2-4,6-7,11,14H,5,9-10H2,1H3
- IUPAC Name
- 3-[(1-phenylpropan-2-yl)amino]propanenitrile
- SMILES
- CC(CC1=CC=CC=C1)NCCC#N
References
- Synthesis Reference
Rohrbach, P. and Blum, J.; U.S. Patent 3,485,924; December 23, 1969; assigned to Manufactures J.R. Bottu (France).
US3485924- General References
- Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. [Article]
- Cody JT, Valtier S: Detection of amphetamine following administration of fenproporex. J Anal Toxicol. 1996 Oct;20(6):425-31. [Article]
- Cohen PA, McCormick D, Casey C, Dawson GF, Hacker KA: Imported compounded diet pill use among Brazilian women immigrants in the United States. J Immigr Minor Health. 2009 Jun;11(3):229-36. Epub 2007 Dec 9. [Article]
- Cohen PA: Imported fenproporex-based diet pills from Brazil: a report of two cases. J Gen Intern Med. 2009 Mar;24(3):430-3. doi: 10.1007/s11606-008-0878-4. [Article]
- Coutts RT, Nazarali AJ, Baker GB, Pasutto FM: Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain. Can J Physiol Pharmacol. 1986 Jun;64(6):724-8. [Article]
- Kraemer T, Theis GA, Weber AA, Maurer HH: Studies on the metabolism and toxicological detection of the amphetamine-like anorectic fenproporex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay. J Chromatogr B Biomed Sci Appl. 2000 Jan 28;738(1):107-18. [Article]
- Rezin GT, Jeremias IC, Ferreira GK, Cardoso MR, Morais MO, Gomes LM, Martinello OB, Valvassori SS, Quevedo J, Streck EL: Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats. Int J Dev Neurosci. 2011 Dec;29(8):937-42. doi: 10.1016/j.ijdevneu.2011.06.007. Epub 2011 Jun 23. [Article]
- Tognoni G, Morselli PL, Garattini S: Amphetamine concentrations in rat brain and human urine after fenproporex administration. Eur J Pharmacol. 1972 Oct;20(1):125-6. [Article]
- Mancini MC, Halpern A: Pharmacological treatment of obesity. Arq Bras Endocrinol Metabol. 2006 Apr;50(2):377-89. Epub 2006 May 23. [Article]
- External Links
- KEGG Drug
- D07947
- PubChem Compound
- 61810
- PubChem Substance
- 46508336
- ChemSpider
- 55690
- 24867
- ChEBI
- 134837
- ChEMBL
- CHEMBL2105566
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Fenproporex
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 20.000 mg Tablet Oral 20.00 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 146 Rohrbach, P. and Blum, J.; U.S. Patent 3,485,924; December 23, 1969; assigned to Manufactures J.R. Bottu (France). - Predicted Properties
Property Value Source Water Solubility 0.184 mg/mL ALOGPS logP 2.14 ALOGPS logP 2.01 Chemaxon logS -3 ALOGPS pKa (Strongest Basic) 7.88 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 35.82 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 58.24 m3·mol-1 Chemaxon Polarizability 22.04 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.996 Blood Brain Barrier + 0.905 Caco-2 permeable + 0.7437 P-glycoprotein substrate Non-substrate 0.5656 P-glycoprotein inhibitor I Non-inhibitor 0.6871 P-glycoprotein inhibitor II Non-inhibitor 0.773 Renal organic cation transporter Inhibitor 0.5146 CYP450 2C9 substrate Non-substrate 0.7702 CYP450 2D6 substrate Substrate 0.7896 CYP450 3A4 substrate Non-substrate 0.7524 CYP450 1A2 substrate Inhibitor 0.6815 CYP450 2C9 inhibitor Non-inhibitor 0.9019 CYP450 2D6 inhibitor Non-inhibitor 0.51 CYP450 2C19 inhibitor Non-inhibitor 0.6544 CYP450 3A4 inhibitor Non-inhibitor 0.703 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8178 Ames test Non AMES toxic 0.8702 Carcinogenicity Non-carcinogens 0.8414 Biodegradation Not ready biodegradable 0.9393 Rat acute toxicity 2.1504 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8172 hERG inhibition (predictor II) Non-inhibitor 0.6721
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-014m-9600000000-4638d290c61f959a86b9 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014u-8900000000-9170971ad830fd7b8183 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00m3-3900000000-53e466643bd3462d072b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-9300000000-5ede4f7d7f15ebd98744 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9500000000-88efd6b54a148307943b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00kf-9200000000-f429e7455f2687652c5e Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-9100000000-207b8205bf88ba5a1e7b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 142.1671 predictedDeepCCS 1.0 (2019) [M+H]+ 144.61674 predictedDeepCCS 1.0 (2019) [M+Na]+ 152.65096 predictedDeepCCS 1.0 (2019)
Drug created at July 31, 2007 13:10 / Updated at February 21, 2021 18:51