Amineptine

Identification

Name
Amineptine
Accession Number
DB04836
Type
Small Molecule
Groups
Illicit, Withdrawn
Description

The Food and Drug Administration suspended the marketing authorisation for Survector in 1999 and France withdrew it from the market, however several developing countries continued to produce it up until 2005.

Structure
Thumb
Synonyms
  • Amineptino
  • Amineptinum
Product Ingredients
IngredientUNIICASInChI Key
Amineptine hydrochlorideA5P604A12R30272-08-3VDPUXONTAVMIKZ-UHFFFAOYSA-N
International/Other Brands
Directim / Maneon / Neolior / Provector / Survector (Servier) / Viaspera
Categories
UNII
27T1I13L6G
CAS number
57574-09-1
Weight
Average: 337.463
Monoisotopic: 337.204179113
Chemical Formula
C22H27NO2
InChI Key
ONNOFKFOZAJDHT-UHFFFAOYSA-N
InChI
InChI=1S/C22H27NO2/c24-21(25)13-3-1-2-8-16-23-22-19-11-6-4-9-17(19)14-15-18-10-5-7-12-20(18)22/h4-7,9-12,22-23H,1-3,8,13-16H2,(H,24,25)
IUPAC Name
N-(6-carboxyhexyl)tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-aminium chloride
SMILES
OC(=O)CCCCCCNC1C2=CC=CC=C2CCC2=CC=CC=C12

Pharmacology

Indication

For the treatment of depression.

Pharmacodynamics

Amineptine is an atypical tricyclic antidepressant.

Mechanism of action

Amineptine selectively inhibits the reuptake of dopamine and to a lesser extent norepinephrine, thus exerting a powerful and fast-acting antidepressant effect.

TargetActionsOrganism
USodium-dependent noradrenaline transporterNot AvailableHuman
USodium-dependent serotonin transporterNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life

48 minutes for the parent drug and 2.5 hours for the metabolites.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Amineptine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Amineptine is combined with (S)-Warfarin.
2,4-thiazolidinedioneAmineptine may decrease the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Amineptine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Amineptine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Amineptine.
3,5-diiodothyropropionic acidThe risk or severity of Cardiac Arrhythmia and CNS stimulation can be increased when 3,5-diiodothyropropionic acid is combined with Amineptine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Amineptine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Amineptine is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineAmineptine may increase the vasopressor activities of 4-Methoxyamphetamine.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Avoid St.John's Wort.
  • Take with food to reduce irritation.

References

Synthesis Reference

Melen,C., Danree, B.and Poignant, J.C.; US.Patent 3,758,528; September 11,1973; assigned to Societe en nom Collectif Science Union et Cie; Societe Francaise de Recherche Medicale. Melen, C., Danree, B. and Poignant, J.C.; U.S. Patent 3,821,249; June 28, 1974; assigned to Societe en nom Collectif Science Union et Cie; Societe Francaise de Recherche Medicale.

US3758528
General References
  1. Vaugeois JM, Corera AT, Deslandes A, Costentin J: Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine uptake inhibitor. Pharmacol Biochem Behav. 1999 Jun;63(2):285-90. [PubMed:10371658]
  2. Grupper C: [New iatrogenic acne: acne caused by amineptin (Survector)]. Ann Dermatol Venereol. 1988;115(11):1174-6. [PubMed:2977079]
  3. Thioly-Bensoussan D, Charpentier A, Triller R, Thioly F, Blanchet P, Tricoire N, Noury JY, Grupper C: [Iatrogenic acne caused by amineptin (Survector). Apropos of 8 cases]. Ann Dermatol Venereol. 1988;115(11):1177-80. [PubMed:2977080]
  4. Vexiau P, Gourmel B, Husson C, Castot A, Rybojad M, Julien R, Fiet J, Puissant A, Cathelineau G: [Severe lesions of acne type induced by chronic amineptin poisoning: apropos of 6 cases]. Ann Dermatol Venereol. 1988;115(11):1180-2. [PubMed:2977081]
  5. Teillac D, Weber MJ, Lowenstein W, de Prost Y: [Acne caused by Survector]. Ann Dermatol Venereol. 1988;115(11):1183-4. [PubMed:2977082]
External Links
KEGG Drug
D07335
PubChem Compound
34869
PubChem Substance
46509012
ChemSpider
32091
BindingDB
50292474
ChEBI
32499
ChEMBL
CHEMBL418995
Therapeutic Targets Database
DCL000340
Wikipedia
Amineptine
ATC Codes
N06AA19 — Amineptine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)226-230Melen,C., Danree, B.and Poignant, J.C.; US.Patent 3,758,528; September 11,1973; assigned to Societe en nom Collectif Science Union et Cie; Societe Francaise de Recherche Medicale Melen, C., Danree, B. and Poignant, J.C.; U.S. Patent 3,821,249; June 28, 1974; assigned to Societe en nom Collectif Science Union et Cie; Societe Francaise de Recherche Medicale
Predicted Properties
PropertyValueSource
Water Solubility1.84e-05 mg/mLALOGPS
logP0.99ALOGPS
logP2.74ChemAxon
logS-7.3ALOGPS
pKa (Strongest Acidic)4.41ChemAxon
pKa (Strongest Basic)9.46ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area53.91 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity112.63 m3·mol-1ChemAxon
Polarizability39.95 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.927
Blood Brain Barrier+0.9384
Caco-2 permeable-0.5548
P-glycoprotein substrateNon-substrate0.5457
P-glycoprotein inhibitor INon-inhibitor0.9324
P-glycoprotein inhibitor IINon-inhibitor0.8538
Renal organic cation transporterNon-inhibitor0.6998
CYP450 2C9 substrateNon-substrate0.7559
CYP450 2D6 substrateNon-substrate0.7653
CYP450 3A4 substrateNon-substrate0.5897
CYP450 1A2 substrateNon-inhibitor0.5434
CYP450 2C9 inhibitorNon-inhibitor0.8792
CYP450 2D6 inhibitorNon-inhibitor0.7593
CYP450 2C19 inhibitorNon-inhibitor0.8446
CYP450 3A4 inhibitorNon-inhibitor0.7073
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9165
Ames testAMES toxic0.6805
CarcinogenicityNon-carcinogens0.8651
BiodegradationNot ready biodegradable0.7096
Rat acute toxicity2.9526 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9341
hERG inhibition (predictor II)Inhibitor0.6018
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on September 12, 2007 03:05 / Updated on November 02, 2018 08:41