Identification
- Generic Name
- Etoperidone
- DrugBank Accession Number
- DB09194
- Background
Etoperidone is an atypical antidepressant introduced in Europe in 1977. It is a phenylpiperazine-substituted triazole derivative with a composition that classifies it as an analog of tradozone and presents a similar pharmacological profile.7 Etoperidone was developed by Angelini Francesco ACRAF.2
- Type
- Small Molecule
- Groups
- Withdrawn
- Structure
Structure for Etoperidone (DB09194)
- Weight
- Average: 377.92
Monoisotopic: 377.1982382 - Chemical Formula
- C19H28ClN5O
- Synonyms
- Etoperidone
- External IDs
- ST-1191
Pharmacology
- Indication
Etoperidone has been studied for the treatment of depression9, tremors in Parkinson, extrapyramidal symptoms12 and male impotence13. It is not certain if it was ever approved and marketed but its current status is withdrawn.
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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
Etoperidone has a biphasic effect on the central transmission of serotonin.7 It presents the capacity to inhibit serotonin receptor but also to inhibit the reuptake of serotonin, norepinephrine and dopamine.8 As part of its actions, etoperidone also inhibits the α-adrenergic receptors which directly corresponds to the sedative and cardiovascular effects.7,10 The presence of both effects caused that the effective dose of etoperidone was poorly tolerated thus, efforts have been made to separate the serotonergic and adrenergic functions in order to generate etoperidone-derivatives like nefazodone.10
- Mechanism of action
The activity of etoperidone is made mainly by its major metabolite 1-(3'-chlorophenyl)piperazine (mCPP). mCPP binds with different affinity to most of the serotonergic receptors and adrenergic receptors. This metabolite is an agonist of 5-HT2c and an antagonist of 5-HT2a. Part of etoperidone structure contibutes to the activity in the α-adrenergic receptors.10
Target Actions Organism A5-hydroxytryptamine receptor 2A antagonistHumans A5-hydroxytryptamine receptor 2C agonistHumans UAlpha-1 adrenergic receptors antagonistHumans UAlpha-2 adrenergic receptors antagonistHumans UDopamine D2 receptor antagonistHumans UMuscarinic acetylcholine receptor antagonistHumans - Absorption
The absorption and bioavailability is highly variable between individuals and can be as low as 12%. The lower bioavailability is explained due to its high metabolism.5 The mean time to peak plasma concentration is ranged from 1.4-4.8 hours.11
- Volume of distribution
The high protein binding presented in etoperidone modulates its volume of distribution to a range of 0.23 to 0.69 L/kg.6
- Protein binding
Etoperidone presents an extensive plasma protein binding.6
- Metabolism
Etoperidone is highly metabolized and it forms 21 different metabolites that can be found in plasma, urine and faeces. The metabolism of etoperidone is thought to be related to 5 different reaction pathways that are alkyl oxidation, piperazinyl oxidation, N-dealkylation, phenyl hydroxylation and conjugation.4
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- Route of elimination
The elimination of an oral dose of etoperidone presents a division of 78.8% found in urine and 9.6% found in faeces. On the elimination route, less than 0.01% of the etoperidone dose is represented by the unchanged drug while the rest is formed by 21 different metabolites.4
- Half-life
After oral administration of etoperidone the terminal half-life was 21.7 hours.4
- Clearance
The apparent clearance of etoperidone was 1.01 ml/min.4
- Adverse Effects
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Etoperidone presented major cardiovascular effects recorded as abnormal electrocardiogram, changes in blood pressure and even cardiac arrest. From the changes in blood pressure hypotension was the primary effect. These cardiovascular reactions are consistent with its effect to catecholamines.5
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Etoperidone is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Etoperidone which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Etoperidone which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Etoperidone which could result in a higher serum level. Acenocoumarol The risk or severity of adverse effects can be increased when Etoperidone is combined with Acenocoumarol. - 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.- Product Ingredients
Ingredient UNII CAS InChI Key Etoperidone hydrochloride 2FSU2FR80J 57775-22-1 BHKPQZVLIZKSAG-UHFFFAOYSA-N - International/Other Brands
- Axiomin (Promeco) / Depracer (L. Lepori, Lda.) / Etoran (II Dong) / Staff (Sigma-Tau)
Categories
- ATC Codes
- N06AB09 — Etoperidone
- Drug Categories
- Antidepressive Agents
- Central Nervous System Depressants
- Combined Inhibitors of Serotonin/Norepinephrine Reuptake
- Drugs that are Mainly Renally Excreted
- Nervous System
- Piperazines
- Psychoanaleptics
- Pyridines
- Pyridones
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Dialkylarylamines / Aniline and substituted anilines / N-alkylpiperazines / Chlorobenzenes / Aryl chlorides / Triazoles / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds show 5 more
- Substituents
- 1,2,4-triazole / Amine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzenoid / Chlorobenzene show 19 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- KAI6MVO39Z
- CAS number
- 52942-31-1
- InChI Key
- IZBNNCFOBMGTQX-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H28ClN5O/c1-3-18-21-25(19(26)24(18)4-2)10-6-9-22-11-13-23(14-12-22)17-8-5-7-16(20)15-17/h5,7-8,15H,3-4,6,9-14H2,1-2H3
- IUPAC Name
- 1-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-3,4-diethyl-4,5-dihydro-1H-1,2,4-triazol-5-one
- SMILES
- CCN1C(=O)N(CCCN2CCN(CC2)C2=CC=CC(Cl)=C2)N=C1CC
References
- General References
- Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article]
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Costa A, Martignoni E, Blandini F, Petraglia F, Genazzani AR, Nappi G: Effects of etoperidone on sympathetic and pituitary-adrenal responses to diverse stressors in humans. Clin Neuropharmacol. 1993 Apr;16(2):127-38. [Article]
- Caldwell GW, Wu WN, Masucci JA: Evaluation of the absorption, excretion and metabolism of [14C] etoperidone in man. Xenobiotica. 2001 Nov;31(11):823-39. doi: 10.1080/00498250110091758 . [Article]
- Lisciani R, Baldini A, Benedetti D, Campana A, Barcellona PS: Acute cardiovascular toxicity of trazodone, etoperidone and imipramine in rats. Toxicology. 1978 Jun;10(2):151-8. [Article]
- He H, Richardson S: Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder CNS Drug Review. 2006 Sept 19;3(1):34-48. [Article]
- Ellis G.P. and West G.B. (1986). Progress in Medicinal Chemistry Volume 23 (pp. 159). Elsevier.
- Morrison-Valfre M. (2016). Foundations of Mental Health Care (pp. 245). Elsevier .
- Taylor and Francis (2000). Index Nominum 2000: International drug directory. Swiss Pharmaceutical Society.
- O'Brien R.A. (1986). Receptor Binding in drug research. Marcel Dekker Inc..
- Barceloux D.G. (2012). Medical toxicology of drug abuse: Synthesized chemicals and psychoactive plants.. Wiley.
- Patents [Link]
- Patents [Link]
- External Links
- PubChem Compound
- 40589
- PubChem Substance
- 310265102
- ChemSpider
- 37083
- BindingDB
- 82438
- ChEBI
- 135589
- ChEMBL
- CHEMBL1743259
- ZINC
- ZINC000003830815
- Wikipedia
- Etoperidone
- MSDS
- Download (79 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Solution / drops Tablet - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 197-198 ºC "Drugs - Synonyms and Properties", Ashgate Publishing Co. boiling point (°C) 499ºC at 760mmHg "Drugs - Synonyms and Properties", Ashgate Publishing Co. - Predicted Properties
Property Value Source Water Solubility 0.425 mg/mL ALOGPS logP 2.81 ALOGPS logP 3.37 Chemaxon logS -3 ALOGPS pKa (Strongest Basic) 7.09 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 42.39 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 106.57 m3·mol-1 Chemaxon Polarizability 42.23 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-a65b1037747704e955b3 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-2009000000-f533bd1da6e3ce3aa04b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0fb9-0029000000-44787853ea3ca94a2d3e Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0ugj-3097000000-f691a119d74fb973be41 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9644000000-fc8d79ac5eb0cd097e49 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000t-0941000000-f5c1f3d52fd107b1e931 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]- 178.3934 predictedDeepCCS 1.0 (2019) [M+H]+ 180.84694 predictedDeepCCS 1.0 (2019) [M+Na]+ 188.85045 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Virus receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Serotonin receptor activity
- Specific Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51820.705 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-1A adrenergic receptor | P35348 |
| Alpha-1B adrenergic receptor | P35368 |
| Alpha-1D adrenergic receptor | P25100 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Components:
| Name | UniProt ID |
|---|---|
| Alpha-2A adrenergic receptor | P08913 |
| Alpha-2B adrenergic receptor | P18089 |
| Alpha-2C adrenergic receptor | P18825 |
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Potassium channel regulator activity
- Specific Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Phosphatidylinositol phospholipase c activity
- Specific Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Components:
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Monoamine transmembrane transporter activity
- Specific Function
- Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A3
- Uniprot ID
- Q01959
- Uniprot Name
- Sodium-dependent dopamine transporter
- Molecular Weight
- 68494.255 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
Drug created at October 16, 2015 21:21 / Updated at February 03, 2022 21:01