You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameZimelidine
Accession NumberDB04832
Typesmall molecule
Groupswithdrawn
Description

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. After its ban, it was succeeded by fluvoxamine and fluoxetine (derived from the antihistamine diphenhydramine) in that order, and the other SSRIs.

Structure
Thumb
Synonyms
SynonymLanguageCode
(Z)-3-(4'-Bromophenyl)-3-(3''-pyridyl)dimethylallylamineNot AvailableNot Available
(Z)-3-[1-(p-Bromophenyl)-3-(dimethylamino)propenyl]pyridineNot AvailableNot Available
(z)-zimelidineNot AvailableNot Available
Cis-zimelidineNot AvailableNot Available
ZimeldineNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number56775-88-3
WeightAverage: 317.224
Monoisotopic: 316.057511201
Chemical FormulaC16H17BrN2
InChI KeyOYPPVKRFBIWMSX-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
[3-(4-bromophenyl)-3-(pyridin-3-yl)prop-2-en-1-yl]dimethylamine
SMILES
CN(C)CC=C(C1=CC=C(Br)C=C1)C1=CN=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenylpropenes
Direct parentPhenylpropenes
Alternative parentsStyrenes; Bromobenzenes; Pyridines and Derivatives; Aryl Bromides; Tertiary Amines; Polyamines; Organobromides
Substituentsstyrene; bromobenzene; aryl halide; aryl bromide; pyridine; tertiary amine; polyamine; organohalogen; organobromide; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropenes. These are compounds containing a phenylpropene moeity, which consists of a propene substituent bound to a phenyl group.
Pharmacology
IndicationFor the treatment of depression.
PharmacodynamicsZimelidine was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants.
Mechanism of actionThe 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half life8.4 +/- 2.0 hours for the parent compound and 19.4 +/- 3.6 hours for norzimelidine.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Inhibitor 0.8949
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate 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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility2.39e-02 g/lALOGPS
logP3.39ALOGPS
logP3.51ChemAxon
logS-4.1ALOGPS
pKa (strongest basic)8.62ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area16.13ChemAxon
rotatable bond count4ChemAxon
refractivity93.94ChemAxon
polarizability30.96ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. 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. Pubmed
  2. 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. Pubmed
External Links
ResourceLink
PubChem Compound5365247
PubChem Substance46504589
ChemSpider38293
WikipediaZimelidine
ATC CodesN06AB02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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
  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
  3. 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. Pubmed

2. Amine oxidase [flavin-containing] B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] B P27338 Details

References:

  1. 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. Pubmed

3. Amine oxidase [flavin-containing] A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

References:

  1. 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. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. 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. Pubmed

Comments
comments powered by Disqus
Drug created on September 11, 2007 15:01 / Updated on September 16, 2013 17:25