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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
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot 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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpropenes. These are compounds containing a phenylpropene moiety, which consists of a propene substituent bound to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropenes
Direct ParentPhenylpropenes
Alternative Parents
Substituents
  • Phenylpropene
  • Styrene
  • Halobenzene
  • Bromobenzene
  • Pyridine
  • Aryl halide
  • Aryl bromide
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
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
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.972
Blood Brain Barrier+0.9382
Caco-2 permeable+0.7284
P-glycoprotein substrateSubstrate0.6049
P-glycoprotein inhibitor INon-inhibitor0.8435
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterInhibitor0.5919
CYP450 2C9 substrateNon-substrate0.8893
CYP450 2D6 substrateNon-substrate0.6656
CYP450 3A4 substrateSubstrate0.5541
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 substrateInhibitor0.8949
CYP450 2D6 substrateInhibitor0.8932
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8185
Ames testNon AMES toxic0.8077
CarcinogenicityNon-carcinogens0.807
BiodegradationNot ready biodegradable0.9964
Rat acute toxicity2.5787 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8348
hERG inhibition (predictor II)Inhibitor0.6614
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0239 mg/mLALOGPS
logP3.39ALOGPS
logP3.51ChemAxon
logS-4.1ALOGPS
pKa (Strongest Basic)8.62ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area16.13 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity93.94 m3·mol-1ChemAxon
Polarizability30.96 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
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
ATC CodesNot Available
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

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Drug created on September 11, 2007 15:01 / Updated on September 16, 2013 17:25