DT-Web

DB00579 - Mazindol


Identification
Name Mazindol
Accession Number DB00579 (APRD01085)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 284.74
Groups approved
Monoisotopic Weight 284.071640755
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.
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
Protein binding Not Available
Biotransformation Hepatic.
Route of elimination 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
Interactions
Drug Interactions
Drug Mechanism of interaction
Acetophenazine Decreased anorexic effect, may increase psychotic symptoms
Chlorpromazine Decreased anorexic effect, may increase psychotic symptoms
Ethopropazine Decreased anorexic effect, may increase psychotic symptoms
Fluoxetine Risk of serotoninergic syndrome
Fluphenazine Decreased anorexic effect, may increase psychotic symptoms
Fluvoxamine Risk of serotoninergic syndrome
Guanethidine Mazindol may decrease the effect of guanethidine.
Isocarboxazid Possible hypertensive crisis
Mesoridazine Decreased anorexic effect, may increase psychotic symptoms
Methdilazine Decreased anorexic effect, may increase psychotic symptoms
Methotrimeprazine Decreased anorexic effect, may increase psychotic symptoms
Paroxetine Risk of serotoninergic syndrome
Perphenazine Decreased anorexic effect, may increase psychotic symptoms
Phenelzine Possible hypertensive crisis
Prochlorperazine Decreased anorexic effect, may increase psychotic symptoms.
Promazine Decreased anorexic effect, may increase psychotic symptoms
Promethazine Decreased anorexic effect, may increase psychotic symptoms.
Propericiazine Decreased anorexic effect, may increase psychotic symptoms.
Propiomazine Decreased anorexic effect, may increase psychotic symptoms
Rasagiline Possible hypertensive crisis
Thiethylperazine Decreased anorexic effect, may increase psychotic symptoms
Thioridazine Decreased anorexic effect, may increase psychotic symptoms
Tranylcypromine Possible hypertensive crisis
Trifluoperazine Decreased anorexic effect, may increase psychotic symptoms
Triflupromazine Decreased anorexic effect, may increase psychotic symptoms
Trimeprazine Decreased anorexic effect, may increase psychotic symptoms
Venlafaxine Risk of serotoninergic syndrome
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


Sodium-dependent noradrenaline transporter
Name Sodium-dependent noradrenaline transporter
Gene Name SLC6A2
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.5753
Sodium-dependent dopamine transporter
Name Sodium-dependent dopamine transporter
Gene Name SLC6A3
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.5299
Sodium-dependent serotonin transporter
Name Sodium-dependent serotonin transporter
Gene Name SLC6A4
Pharmacological action yes
Actions inhibitor
References
  • 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
DTHybrid score 0.4147

Predictions


Id Partner name Gene Name Score
4119 Cytochrome P450 2D6 CYP2D6 0.1761
4512 Cytochrome P450 3A4 CYP3A4 0.1006
556 Alpha-1A adrenergic receptor ADRA1A 0.0878
131 Synaptic vesicular amine transporter SLC18A2 0.086
3941 Amine oxidase [flavin-containing] A MAOA 0.0788
3939 Amine oxidase [flavin-containing] B MAOB 0.0664
6016 Cytochrome P450 2C19 CYP2C19 0.0615
492 Histamine H1 receptor HRH1 0.0614
1588 Multidrug resistance protein 1 ABCB1 0.0601
502 5-hydroxytryptamine 2A receptor HTR2A 0.0563
4200 Cytochrome P450 1A2 CYP1A2 0.0554
318 Alpha-2A adrenergic receptor ADRA2A 0.0546
632 Alpha-1B adrenergic receptor ADRA1B 0.0515
4757 Cytochrome P450 2C9 CYP2C9 0.0483
590 5-hydroxytryptamine 2C receptor HTR2C 0.0482
6030 Cytochrome P450 2B6 CYP2B6 0.046
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0425
1181 Alpha-1-acid glycoprotein 1 ORM1 0.033
436 5-hydroxytryptamine 2B receptor HTR2B 0.0323
1636 Trace amine-associated receptor 1 TAAR1 0.0313
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.026
629 Alpha-2B adrenergic receptor ADRA2B 0.0256
4118 Cytochrome P450 3A5 CYP3A5 0.0254
6013 Cytochrome P450 2E1 CYP2E1 0.0231
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0219
320 5-hydroxytryptamine 1A receptor HTR1A 0.0218
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0213
6107 Cytochrome P450 3A7 CYP3A7 0.0207
193 Beta-1 adrenergic receptor ADRB1 0.0205
766 Beta-2 adrenergic receptor ADRB2 0.0201
4924 Cytochrome P450 2C8 CYP2C8 0.0188
1656 CYP2B protein CYP2B 0.0187
378 Alpha-2C adrenergic receptor ADRA2C 0.0187
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0179
6144 Solute carrier family 22 member 2 SLC22A2 0.0177
6147 Solute carrier family 22 member 3 SLC22A3 0.0172
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0172
341 5-hydroxytryptamine 3 receptor HTR3A 0.0171
831 D(2) dopamine receptor DRD2 0.0155
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0154
450 Muscarinic acetylcholine receptor M4 CHRM4 0.015
118 Organic cation/carnitine transporter 2 SLC22A5 0.0142
1517 Beta-3 adrenergic receptor ADRB3 0.0138
3923 Cholinesterase BCHE 0.0136
23 D(1A) dopamine receptor DRD1 0.0133
789 Alpha-1D adrenergic receptor ADRA1D 0.0132
6145 Solute carrier family 22 member 1 SLC22A1 0.013
5718 Cytochrome P450 2A6 CYP2A6 0.0116
6432 Transporter snf 0.0111
467 Delta-type opioid receptor OPRD1 0.0104
696 Kappa-type opioid receptor OPRK1 0.0104
1757 Myeloperoxidase MPO 0.0103
6106 Cytochrome P450 2C18 CYP2C18 0.0096
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0096
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.0095
6182 Cytochrome P450 2J2 CYP2J2 0.0086
847 Mu-type opioid receptor OPRM1 0.0084
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0075
587 Serum albumin ALB 0.0074
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0073
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0072
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.007
474 Acetylcholinesterase ACHE 0.0069
6024 Cytochrome P450 1A1 CYP1A1 0.0065
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0065
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0063
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0061
6164 POU domain, class 5, transcription factor 1 POU5F1 0.006
4120 NADPH--cytochrome P450 reductase POR 0.0057
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0052
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0052
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0047
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0046
2981 Phospholipase A2, membrane associated PLA2G2A 0.0044
828 Phenylalanine-4-hydroxylase PAH 0.0043
3109 Phenylalanine-4-hydroxylase phhA 0.0043
904 Glutathione S-transferase P GSTP1 0.0042
833 Organic cation/carnitine transporter 1 SLC22A4 0.0042
482 Glycine receptor subunit alpha-1 GLRA1 0.004
94 5-hydroxytryptamine 4 receptor HTR4 0.0037
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0036
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0036
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0036
1360 Sphingomyelin phosphodiesterase SMPD1 0.0036
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0033
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0031
319 Opioid receptor, sigma 1 OPRS1 0.0031
174 Sigma 1-type opioid receptor SIGMAR1 0.0026
153 Dopamine beta-hydroxylase DBH 0.0025
1618 High affinity nerve growth factor receptor NTRK1 0.0025
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0024
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0024
124 Histamine H2 receptor HRH2 0.0022
3810 Catechol O-methyltransferase COMT 0.002
163 D(1B) dopamine receptor DRD5 0.0019
725 5-hydroxytryptamine 1D receptor HTR1D 0.0019
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0019
885 5-hydroxytryptamine 1B receptor HTR1B 0.0019
20 Prostaglandin G/H synthase 1 PTGS1 0.0018
432 D(4) dopamine receptor DRD4 0.0018
638 D(3) dopamine receptor DRD3 0.0018
6151 Monocarboxylate transporter 10 SLC16A10 0.0018
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.001
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.001
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.001
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0009
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0009
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0009
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0009
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0009
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0009
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0008
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0008
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0008
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0008
6148 Multidrug resistance-associated protein 7 ABCC10 0.0007
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0007
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0007
776 Bile salt export pump ABCB11 0.0006
2164 Multidrug resistance-associated protein 4 ABCC4 0.0006
862 Multidrug resistance-associated protein 1 ABCC1 0.0006
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0006
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0006
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0005
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