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Identification
Name Mazindol
Accession Number DB00579 (APRD01085)
Type small molecule
Groups approved
Description

Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • DEA No. 1605
  • Dimagrir
  • Magrilon
  • Mazanor
  • Mazildene
  • Mazindol [USAN:BAN:INN]
  • Mazindolum [INN-Latin]
  • Sanorex
  • Terenac
  • Teronac
Brand name mixtures Not Available
Categories
  • Dopamine Uptake Inhibitors
  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
CAS number 22232-71-9
Weight Average: 284.74
Monoisotopic: 284.071640755
Chemical Formula C16H13ClN2O
InChI Key InChIKey=ZPXSCAKFGYXMGA-UHFFFAOYSA-N
InChI
InChI=1S/C16H13ClN2O/c17-12-7-5-11(6-8-12)16(20)14-4-2-1-3-13(14)15-18-9-10-19(15)16/h1-8,20H,9-10H2
Plain Text
IUPAC Name
5-(4-chlorophenyl)-2H,3H,5H-imidazo[2,1-a]isoindol-5-ol
SMILES
OC1(N2CCN=C2C2=C1C=CC=C2)C1=CC=C(Cl)C=C1
Plain Text
Mass Spec show (8.1 KB)
Taxonomy
Kingdom Organic
Classes
  • Benzyl Alcohols and Derivatives
  • Indoles and Indole Derivatives
Substructures
  • Hydroxy Compounds
  • Imidazolines
  • Carboxylic Acids and Derivatives
  • Benzyl Alcohols and Derivatives
  • Benzene and Derivatives
  • Aminals and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Imidazoles
  • Indoles and Indole Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamidines
  • Imines
  • Pyrrolines
Pharmacology
Indication Used in short-term (a few weeks) treatment of exogenous obesity in conjunction with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a body mass index of 30 kg of body weight per height in meters squared (kg/m2) or in patients with a body mass index of 27 kg/m2 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia.
Pharmacodynamics Mazindol is a sympathomimetic amine, which is similar to an amphetamine. Mazindol stimulates the central nervous system (nerves and brain), which increases your heart rate and blood pressure and decreases your appetite. Sympathomimetic appetite suppressants are used in the short-term treatment of obesity. Their appetite-reducing effect tends to decrease after a few weeks. Because of this, these medicines are useful only during the first few weeks of a weight-loss program.
Mechanism of action Although the mechanism of action of the sympathomimetics in the treatment of obesity is not fully known, these medications have pharmacological effects similar to those of amphetamines. Unlike other sympathomimetic appetite suppressants such as phentermine, mazindol is thought to inhibit the reuptake of norepinephrine rather than to cause its release.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life 10-13 hours
Clearance Not Available
Toxicity Symptoms of a mazindol overdose include restlessness, tremor, rapid breathing, confusion, hallucinations, panic, aggressiveness, nausea, vomiting, diarrhea, an irregular heartbeat, and seizures.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Wyeth ayerst laboratories
  • Novartis pharmaceuticals corp
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 3.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.39e-01 g/l ALOGPS
logP 2.64 ALOGPS
logP 3.44 ChemAxon Molconvert
logS -3.31 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 35.83 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 79.42 ChemAxon Molconvert
polarizability 29.42 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00367 Link_out
PubChem Compound 4020 Link_out
PubChem Substance 46509094 Link_out
ChemSpider 3880 Link_out
BindingDB 50005536 Link_out
Therapeutic Targets Database DAP000722 Link_out
PharmGKB PA450326 Link_out
Drug Product Database 432407 Link_out
Drugs.com http://www.drugs.com/mtm/mazindol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mazindol Link_out
ATC Codes
  • A08AA05
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • If product causes GI problems, it can be taken during meals.
  • May be taken without regard to meals, but preferably 1 hour before a meal.
Targets

1. Sodium-dependent noradrenaline transporter

Pharmacological action: yes
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Raffel DM, Chen W: Binding of [3H]mazindol to cardiac norepinephrine transporters: kinetic and equilibrium studies. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jul;370(1):9-16. Epub 2004 Jul 22. Pubmed
  2. Raffel DM, Chen W, Sherman PS, Gildersleeve DL, Jung YW: Dependence of cardiac 11C-meta-hydroxyephedrine retention on norepinephrine transporter density. J Nucl Med. 2006 Sep;47(9):1490-6. Pubmed
  3. Zhao L, Johnson KM, Zhang M, Flippen-Anderson J, Kozikowski AP: Chemical synthesis and pharmacology of 6- and 7-hydroxylated 2-carbomethoxy-3-(p-tolyl)tropanes: antagonism of cocaine’s locomotor stimulant effects. J Med Chem. 2000 Aug 24;43(17):3283-94. Pubmed
  4. Ritz MC, Boja JW, Grigoriadis D, Zaczek R, Carroll FI, Lewis AH, Kuhar MJ: [3H]WIN 35,065-2: a ligand for cocaine receptors in striatum. J Neurochem. 1990 Nov;55(5):1556-62. Pubmed
  5. Sharpe IA, Palant E, Schroeder CI, Kaye DM, Adams DJ, Alewood PF, Lewis RJ: Inhibition of the norepinephrine transporter by the venom peptide chi-MrIA. Site of action, Na+ dependence, and structure-activity relationship. J Biol Chem. 2003 Oct 10;278(41):40317-23. Epub 2003 Jul 28. Pubmed
  6. 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. Sodium-dependent dopamine transporter

Pharmacological action: yes
Actions: inhibitor

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Itzhak Y, Martin JL: Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity: cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine transporter binding sites. Brain Res. 1999 Feb 13;818(2):204-11. Pubmed
  2. Saunders C, Ferrer JV, Shi L, Chen J, Merrill G, Lamb ME, Leeb-Lundberg LM, Carvelli L, Javitch JA, Galli A: Amphetamine-induced loss of human dopamine transporter activity: an internalization-dependent and cocaine-sensitive mechanism. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6850-5. Pubmed
  3. Goettl VM, Wemlinger TA, Fong TG, Neff NH, Hadjiconstantinou M: Retinal cholinergic and dopaminergic deficits of aged rats are improved following treatment with GM1 ganglioside. Brain Res. 2000 Sep 15;877(1):1-6. Pubmed
  4. Tidjane Corera A, Do-Rego JC, Costentin J, Bonnet JJ: Differential sensitivity to NaCl for inhibitors and substrates that recognize mutually exclusive binding sites on the neuronal transporter of dopamine in rat striatal membranes. Neurosci Res. 2001 Mar;39(3):319-25. Pubmed
  5. Purkerson-Parker S, McDaniel KL, Moser VC: Dopamine transporter binding in the rat striatum is increased by gestational, perinatal, and adolescent exposure to heptachlor. Toxicol Sci. 2001 Dec;64(2):216-23. Pubmed
  6. 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
  7. Kulkarni SS, Newman AH, Houlihan WJ: Three-dimensional quantitative structure-activity relationships of mazindol analogues at the dopamine transporter. J Med Chem. 2002 Sep 12;45(19):4119-27. Pubmed
  8. Houlihan WJ, Kelly L, Pankuch J, Koletar J, Brand L, Janowsky A, Kopajtic TA: Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter. J Med Chem. 2002 Sep 12;45(19):4097-109. Pubmed

3. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

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:
  1. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:40

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.