DrugBank: Zimelidine (DB04832)

targets (3) transporters (1)

Identification

Name

Zimelidine

Accession Number

DB04832

Type

small molecule

Groups

withdrawn

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

(Z)-3-(4'-Bromophenyl)-3-(3''-pyridyl)dimethylallylamine
(Z)-3-[1-(p-Bromophenyl)-3-(dimethylamino)propenyl]pyridine
(z)-zimelidine
Cis-zimelidine
Zimeldine

Salts

Not Available

Brand names

Not Available

Brand mixtures

Not Available

Categories

Selective Serotonin Reuptake Inhibitors (SSRIs)
Antidepressive Agents
Serotonin Uptake Inhibitors

CAS number

56775-88-3

Weight

Average: 317.224
Monoisotopic: 316.057511201

Chemical Formula

C₁₆H₁₇BrN₂

InChI Key

InChIKey=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-

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Not Available

Classes

Not Available

Substructures

Not Available

Pharmacology

Indication

For the treatment of depression.

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.

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

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

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	2.39e-02 g/l	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	ChemAxon
rotatable bond count	4	ChemAxon
refractivity	93.94	ChemAxon
polarizability	30.96	ChemAxon

References

Synthesis Reference

Not Available

General Reference

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
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

Resource	Link
PubChem Compound	5365247
PubChem Substance	46504589
ChemSpider	38293
Wikipedia	http://en.wikipedia.org/wiki/Zimelidine

ATC Codes

N06AB02

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Sodium-dependent serotonin transporter Pharmacological action: unknown Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals Organism class: human UniProt ID: P31645 Gene: SLC6A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 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 Pharmacological action: unknown Actions: inhibitor 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 tissues. MAOB preferentially degrades benzylamine and phenylethylamine Organism class: human UniProt ID: P27338 Gene: MAOB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Pubmed 3. Amine oxidase [flavin-containing] A Pharmacological action: unknown Actions: inhibitor 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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine Organism class: human UniProt ID: P21397 Gene: MAOA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Pubmed

Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: unknown

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out

Gene: SLC6A4 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
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

Pharmacological action: unknown
Actions: inhibitor

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 tissues. MAOB preferentially degrades benzylamine and phenylethylamine

Organism class: human
UniProt ID: P27338 Link_out

Gene: MAOB Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

3. Amine oxidase [flavin-containing] A

Pharmacological action: unknown
Actions: inhibitor

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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

Organism class: human
UniProt ID: P21397 Link_out

Gene: MAOA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

Transporters
1. Multidrug resistance protein 1 Actions: inhibitor Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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. Pubmed

Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

Comments

Drug created on September 11, 2007 15:01 / Updated on February 08, 2013 16:23