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Identification
NameMazindol
Accession NumberDB00579  (APRD01085)
TypeSmall Molecule
GroupsApproved
Description

Mazindol is a 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. Mazindol is only approved in the United States for the treatment of Duchenne muscular dystrophy, and is not marketed or available in the United States for use in the treatment of obesity.

Structure
Thumb
Synonyms
Mazindol
Mazindolo
Mazindolum
Sanorex
External Identifiers
  • 42-548
  • AN 488
  • DEA No. 1605
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sanorextablet2 mgoralHexim Pharmaceuticals Inc1975-12-31Not applicableCanada
Sanorextablet1 mgoralHexim Pharmaceuticals Inc1980-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DimagrirGador
Fagolip PlusCetus
MazanorKwang Dong
TeronacNovartis
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIC56709M5NH
CAS number22232-71-9
WeightAverage: 284.74
Monoisotopic: 284.071640755
Chemical FormulaC16H13ClN2O
InChI KeyInChIKey=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
IUPAC Name
5-(4-chlorophenyl)-2H,3H,5H-imidazo[2,1-a]isoindol-5-ol
SMILES
OC1(N2CCN=C2C2=CC=CC=C12)C1=CC=C(Cl)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as isoindoles. These are heteropolycyclic compounds with a structure containing isoindole, a benzo-fused pyrrole.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoindoles and derivatives
Sub ClassIsoindoles
Direct ParentIsoindoles
Alternative Parents
Substituents
  • Isoindole
  • Isoindoline
  • Halobenzene
  • Chlorobenzene
  • Imidolactam
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • 2-imidazoline
  • Tertiary amine
  • Azacycle
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Carboxylic acid amidine
  • Amidine
  • Alkanolamine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed 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.
PharmacodynamicsMazindol 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 actionAlthough 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half life10-13 hours
ClearanceNot Available
ToxicitySymptoms 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9793
Blood Brain Barrier+0.9757
Caco-2 permeable+0.5286
P-glycoprotein substrateSubstrate0.5816
P-glycoprotein inhibitor INon-inhibitor0.7523
P-glycoprotein inhibitor IIInhibitor0.7127
Renal organic cation transporterInhibitor0.7465
CYP450 2C9 substrateNon-substrate0.7257
CYP450 2D6 substrateNon-substrate0.7107
CYP450 3A4 substrateSubstrate0.6461
CYP450 1A2 substrateInhibitor0.615
CYP450 2C9 inhibitorInhibitor0.5
CYP450 2D6 inhibitorInhibitor0.5
CYP450 2C19 inhibitorInhibitor0.527
CYP450 3A4 inhibitorNon-inhibitor0.7389
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.542
Ames testNon AMES toxic0.6859
CarcinogenicityNon-carcinogens0.8924
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1216 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9837
hERG inhibition (predictor II)Inhibitor0.5621
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Wyeth ayerst laboratories
  • Novartis pharmaceuticals corp
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral1 mg
Tabletoral2 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point198-199U.S. Patents 3,597,445 and 3,763,178.
logP3.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.139 mg/mLALOGPS
logP2.64ALOGPS
logP3.44ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)11.61ChemAxon
pKa (Strongest Basic)3.86ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area35.83 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity79.42 m3·mol-1ChemAxon
Polarizability29.42 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.08 KB)
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-014i-0390000000-2514253f04060882685bView in MoNA
References
Synthesis Reference

U.S. Patents 3,597,445 and 3,763,178.

US3597445
General ReferencesNot Available
External Links
ATC CodesA08AA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
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:15300361 ]
  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:16954558 ]
  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:10966747 ]
  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:2120386 ]
  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:12885787 ]
  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:9537821 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
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:10082805 ]
  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:10823899 ]
  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:10980236 ]
  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:11248372 ]
  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:11719704 ]
  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:9537821 ]
  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:12213055 ]
  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:12213053 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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 the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin an...
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
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:9537821 ]
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Drug created on June 13, 2005 07:24 / Updated on May 23, 2014 11:58