Zimelidine
Identification
- Generic Name
- Zimelidine
- DrugBank Accession Number
- DB04832
- Background
Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome and due to a peculiar hypersensitivity reaction involving many organs including skin exanthema, flu-like symptoms, arthralgias, and sometimes eosinophilia. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients.
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Structure
- Weight
- Average: 317.23
Monoisotopic: 316.057512 - Chemical Formula
- C16H17BrN2
- Synonyms
- (Z)-3-(4'-Bromophenyl)-3-(3''-pyridyl)dimethylallylamine
- (Z)-zimelidine
- cis-zimelidine
- Zimeldina
- Zimeldine
- Zimeldinum
Pharmacology
- Indication
For the treatment of depression.
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- Pharmacodynamics
Zimelidine was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants.
- Mechanism of action
The antidepressant actions of zimelidine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Zimelidine blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
Target Actions Organism UAmine oxidase [flavin-containing] B inhibitorHumans UAmine oxidase [flavin-containing] A inhibitorHumans USodium-dependent serotonin transporter Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
8.4 +/- 2.0 hours for the parent compound and 19.4 +/- 3.6 hours for norzimelidine.
- Clearance
Not Available
- 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 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 adverse effects can be increased when 1,2-Benzodiazepine is combined with Zimelidine. Abciximab The risk or severity of hemorrhage can be increased when Zimelidine is combined with Abciximab. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Zimelidine. Abiraterone The metabolism of Abiraterone can be decreased when combined with Zimelidine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Zimelidine. - 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 Zimelidine hydrochloride 7GLK27586K 60525-15-7 GELMUARXROJGSO-LFMIJCLESA-N
Categories
- ATC Codes
- N06AB02 — Zimeldine
- Drug Categories
- Antidepressive Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (moderate)
- Cytochrome P-450 Enzyme Inhibitors
- Hypoglycemia-Associated Agents
- Membrane Transport Modulators
- Monoamine Oxidase A Inhibitors for interaction with Monoamine Oxidase A substrates
- Nervous System
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- P-glycoprotein inhibitors
- Psychoanaleptics
- Pyridines
- Selective Serotonin Reuptake Inhibitors
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as styrenes. These are organic compounds containing an ethenylbenzene moiety.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Styrenes
- Direct Parent
- Styrenes
- Alternative Parents
- Bromobenzenes / Pyridines and derivatives / Aryl bromides / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organobromides / Hydrocarbon derivatives
- Substituents
- Amine / Aromatic heteromonocyclic compound / Aryl bromide / Aryl halide / Azacycle / Bromobenzene / Halobenzene / Heteroaromatic compound / Hydrocarbon derivative / Organic nitrogen compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 3J928617DW
- CAS number
- 56775-88-3
- InChI Key
- OYPPVKRFBIWMSX-SXGWCWSVSA-N
- InChI
- InChI=1S/C16H17BrN2/c1-19(2)11-9-16(14-4-3-10-18-12-14)13-5-7-15(17)8-6-13/h3-10,12H,11H2,1-2H3/b16-9-
- IUPAC Name
- [(2Z)-3-(4-bromophenyl)-3-(pyridin-3-yl)prop-2-en-1-yl]dimethylamine
- SMILES
- CN(C)C\C=C(\C1=CC=C(Br)C=C1)C1=CC=CN=C1
References
- General References
- Caille G, Kouassi E, de Montigny C: Pharmacokinetic study of zimelidine using a new GLC method. Clin Pharmacokinet. 1983 Nov-Dec;8(6):530-40. [Article]
- Godbout R, Montplaisir J: The effect of zimelidine, a serotonin-reuptake blocker, on cataplexy and daytime sleepiness of narcoleptic patients. Clin Neuropharmacol. 1986;9(1):46-51. [Article]
- External Links
- PubChem Compound
- 41987
- PubChem Substance
- 46504589
- ChemSpider
- 4517305
- BindingDB
- 50020706
- ChEBI
- 135357
- ChEMBL
- CHEMBL37744
- ZINC
- ZINC000008099545
- Wikipedia
- Zimelidine
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
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0239 mg/mL ALOGPS logP 3.39 ALOGPS logP 3.51 Chemaxon logS -4.1 ALOGPS pKa (Strongest Basic) 8.62 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 16.13 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 93.94 m3·mol-1 Chemaxon Polarizability 30.94 Å3 Chemaxon Number of Rings 2 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 + 0.972 Blood Brain Barrier + 0.9382 Caco-2 permeable + 0.7284 P-glycoprotein substrate Substrate 0.6049 P-glycoprotein inhibitor I Non-inhibitor 0.8435 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Inhibitor 0.5919 CYP450 2C9 substrate Non-substrate 0.8893 CYP450 2D6 substrate Non-substrate 0.6656 CYP450 3A4 substrate Substrate 0.5541 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Inhibitor 0.8949 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.796 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8185 Ames test Non AMES toxic 0.8077 Carcinogenicity Non-carcinogens 0.807 Biodegradation Not ready biodegradable 0.9964 Rat acute toxicity 2.5787 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8348 hERG inhibition (predictor II) Inhibitor 0.6614
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014j-4049000000-6800d04f91c49d1f8562 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0019000000-64b8f0aec0727c34a7fa Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-3195000000-4cb6c93a6e9aca55bd20 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-3192000000-23444cb321e4e3ba731b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001l-1930000000-2aca4e1f1742bd3ec1d7 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9020000000-999395d801aab66c75cd 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]- 167.29697 predictedDeepCCS 1.0 (2019) [M+H]+ 169.65497 predictedDeepCCS 1.0 (2019) [M+Na]+ 176.24806 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Primary amine oxidase activity
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOB
- Uniprot ID
- P27338
- Uniprot Name
- Amine oxidase [flavin-containing] B
- Molecular Weight
- 58762.475 Da
References
- Egashira T, Takayama F, Yamanaka Y: The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species. Jpn J Pharmacol. 1999 Sep;81(1):115-21. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
References
- Egashira T, Takayama F, Yamanaka Y: Effects of long-term treatment with dicyclic, tricyclic, tetracyclic, and noncyclic antidepressant drugs on monoamine oxidase activity in mouse brain. Gen Pharmacol. 1996 Jul;27(5):773-8. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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]
- Sugimoto Y, Inoue K, Yamada J: Involvement of serotonin in zimelidine-induced hyperglycemia in mice. Biol Pharm Bull. 1999 Nov;22(11):1240-1. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Gerotziafas GT, Mahe I, Elalamy I: New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients. Ther Clin Risk Manag. 2014 Jun 13;10:423-36. doi: 10.2147/TCRM.S49063. eCollection 2014. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [Article]
Drug created at September 11, 2007 21:01 / Updated at June 12, 2020 16:52