DT-Web

DB01579 - Phendimetrazine


Identification
Name Phendimetrazine
Accession Number DB01579
Type small molecule
Description Phendimetrazine is a weight loss medication. Phendimetrazine is chemically related to amphetamines and is a Schedule III drug under the Convention on Psychotropic Substances. In the United States, phendimetrazine is a Schedule III controlled substance under the Uniform Controlled Substances Act of 1970.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 191.2695
Groups illicit
Monoisotopic Weight 191.131014171
Pharmacology
Indication Used in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction.
Mechanism of action Phendimetrazine may act in a similar way to amphetamines in that it activates the alpha-adrenergic system to induce an appetite suppressive and metabolic increase effect. The drug also acts as a norepinephrine-dopamine releasing agent (NDRA). It can bind to and reverse the NET.
Absorption Peak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours.
Protein binding Not Available
Biotransformation Approximately 30% of a given dose of phendimetrazine is metabolized into phenmetrazine, which may account for part of its anorectic effect, and probably also influences abuse potential; individuals who metabolise a greater proportion of phendimetrazine into phenmetrazine are more likely to develop problems with dependence and addiction
Route of elimination The major route of elimination is via the kidneys where most of the drug and metabolites are excreted.
Toxicity Acute overdosage of phendimetrazine may manifest itself by the following signs and symptoms: unusual restlessness, confusion, belligerance, hallucinations, and panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Poisoning may result in convulsions, coma and death.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Chlorpromazine Decreased anorexic effect, may increases psychotic symptoms
Fluoxetine Risk of serotoninergic syndrome
Fluphenazine Decreased anorexic effect, may increase psychotic symptoms
Fluvoxamine Risk of serotoninergic syndrome
Guanethidine Phendimetrazine may decrease the effect of guanethidine.
Isocarboxazid Possible hypertensive crisis
Mesoridazine 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 pyschotic symptoms
Promethazine Decreased anorexic effect, may increase pyschotic symptoms
Propericiazine Decreased anorexic effect, may increase pyschotic symptoms
Rasagiline Possible hypertensive crisis
Thioridazine Decreased anorexic effect, may increase psychotic symptoms
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trandolapril Phendimetrazine may reduce the efficacy of Trandolapril.
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of the amphetamine, Phendimetrazine. Concomitant therapy should be avoided.
Trifluoperazine Decreased anorexic effect, may increase psychotic symptoms
Triprolidine Triprolidine may reduce the sedative effect of the antihistamine, Phendimetrazine.
Food Interactions Not Available

Targets


Alpha-1A adrenergic receptor
Name Alpha-1A adrenergic receptor
Gene Name ADRA1A
Pharmacological action yes
Actions agonist
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
  • Bray GA: Drug Insight: appetite suppressants. Nat Clin Pract Gastroenterol Hepatol. 2005 Feb;2(2):89-95. - Pubmed
  • Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. - Pubmed
  • Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. - Pubmed
DTHybrid score 0.4183
Sodium-dependent noradrenaline transporter
Name Sodium-dependent noradrenaline transporter
Gene Name SLC6A2
Pharmacological action yes
Actions negative modulator
References
  • Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. - Pubmed
DTHybrid score 0.3726
Alpha-1B adrenergic receptor
Name Alpha-1B adrenergic receptor
Gene Name ADRA1B
Pharmacological action unknown
Actions agonist
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
  • Bray GA: Drug Insight: appetite suppressants. Nat Clin Pract Gastroenterol Hepatol. 2005 Feb;2(2):89-95. - Pubmed
  • Bray GA: A concise review on the therapeutics of obesity. Nutrition. 2000 Oct;16(10):953-60. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. - Pubmed
DTHybrid score 0.283

Predictions


Id Partner name Gene Name Score
713 Sodium-dependent dopamine transporter SLC6A3 0.1442
824 Sodium-dependent serotonin transporter SLC6A4 0.1376
318 Alpha-2A adrenergic receptor ADRA2A 0.1303
789 Alpha-1D adrenergic receptor ADRA1D 0.1284
4119 Cytochrome P450 2D6 CYP2D6 0.1248
4512 Cytochrome P450 3A4 CYP3A4 0.0946
502 5-hydroxytryptamine 2A receptor HTR2A 0.0835
831 D(2) dopamine receptor DRD2 0.0701
23 D(1A) dopamine receptor DRD1 0.0674
1588 Multidrug resistance protein 1 ABCB1 0.0669
629 Alpha-2B adrenergic receptor ADRA2B 0.0595
492 Histamine H1 receptor HRH1 0.0551
131 Synaptic vesicular amine transporter SLC18A2 0.0539
4200 Cytochrome P450 1A2 CYP1A2 0.0525
378 Alpha-2C adrenergic receptor ADRA2C 0.0482
320 5-hydroxytryptamine 1A receptor HTR1A 0.0482
590 5-hydroxytryptamine 2C receptor HTR2C 0.0469
766 Beta-2 adrenergic receptor ADRB2 0.0408
193 Beta-1 adrenergic receptor ADRB1 0.0406
103 Muscarinic acetylcholine receptor M1 CHRM1 0.04
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0382
6016 Cytochrome P450 2C19 CYP2C19 0.0372
3941 Amine oxidase [flavin-containing] A MAOA 0.0332
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0324
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0316
51 Muscarinic acetylcholine receptor M3 CHRM3 0.03
4757 Cytochrome P450 2C9 CYP2C9 0.0295
617 Muscarinic acetylcholine receptor M2 CHRM2 0.029
432 D(4) dopamine receptor DRD4 0.0279
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0276
6145 Solute carrier family 22 member 1 SLC22A1 0.0265
6030 Cytochrome P450 2B6 CYP2B6 0.0236
725 5-hydroxytryptamine 1D receptor HTR1D 0.0229
638 D(3) dopamine receptor DRD3 0.021
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0206
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0206
6013 Cytochrome P450 2E1 CYP2E1 0.0205
4118 Cytochrome P450 3A5 CYP3A5 0.0203
1636 Trace amine-associated receptor 1 TAAR1 0.019
885 5-hydroxytryptamine 1B receptor HTR1B 0.0181
1256 5-hydroxytryptamine 6 receptor HTR6 0.0173
3939 Amine oxidase [flavin-containing] B MAOB 0.0167
6144 Solute carrier family 22 member 2 SLC22A2 0.0167
587 Serum albumin ALB 0.0167
163 D(1B) dopamine receptor DRD5 0.0167
828 Phenylalanine-4-hydroxylase PAH 0.0164
3109 Phenylalanine-4-hydroxylase phhA 0.0164
1517 Beta-3 adrenergic receptor ADRB3 0.0154
716 5-hydroxytryptamine 7 receptor HTR7 0.015
436 5-hydroxytryptamine 2B receptor HTR2B 0.0145
6107 Cytochrome P450 3A7 CYP3A7 0.0143
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0142
6147 Solute carrier family 22 member 3 SLC22A3 0.014
3923 Cholinesterase BCHE 0.0132
4924 Cytochrome P450 2C8 CYP2C8 0.0115
6138 Multidrug resistance protein 3 ABCB4 0.0113
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0102
341 5-hydroxytryptamine 3 receptor HTR3A 0.01
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0099
528 5-hydroxytryptamine 1E receptor HTR1E 0.0097
118 Organic cation/carnitine transporter 2 SLC22A5 0.0093
6024 Cytochrome P450 1A1 CYP1A1 0.0092
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0086
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0086
474 Acetylcholinesterase ACHE 0.0077
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0076
6432 Transporter snf 0.0071
465 Calmodulin CALM1 0.007
1656 CYP2B protein CYP2B 0.0067
124 Histamine H2 receptor HRH2 0.006
467 Delta-type opioid receptor OPRD1 0.0055
696 Kappa-type opioid receptor OPRK1 0.0055
6151 Monocarboxylate transporter 10 SLC16A10 0.005
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0048
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0047
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0046
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0046
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0046
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0046
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0045
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0044
2981 Phospholipase A2, membrane associated PLA2G2A 0.0044
1757 Myeloperoxidase MPO 0.0044
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0042
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0042
6182 Cytochrome P450 2J2 CYP2J2 0.0041
847 Mu-type opioid receptor OPRM1 0.004
482 Glycine receptor subunit alpha-1 GLRA1 0.004
5718 Cytochrome P450 2A6 CYP2A6 0.0038
3426 Glutamine synthetase glnA 0.0037
3987 Glutamine synthetase GLUL 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
233 Potassium channel subfamily K member 2 KCNK2 0.0036
6859 Protein S100-A4 S100A4 0.0035
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0034
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0033
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0032
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0031
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0031
6106 Cytochrome P450 2C18 CYP2C18 0.003
4120 NADPH--cytochrome P450 reductase POR 0.003
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0029
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0029
1360 Sphingomyelin phosphodiesterase SMPD1 0.0029
833 Organic cation/carnitine transporter 1 SLC22A4 0.0029
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0028
3947 Xanthine dehydrogenase/oxidase XDH 0.0028
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0028
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0028
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0028
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0027
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0027
776 Bile salt export pump ABCB11 0.0026
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0026
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0024
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0024
20 Prostaglandin G/H synthase 1 PTGS1 0.0023
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0023
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0022
904 Glutathione S-transferase P GSTP1 0.002
1618 High affinity nerve growth factor receptor NTRK1 0.002
164 Histamine H4 receptor HRH4 0.0019
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0019
1374 Natriuretic peptides B NPPB 0.0019
1827 Gap junction alpha-1 protein GJA1 0.0019
1908 Vascular cell adhesion protein 1 VCAM1 0.0019
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0016
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0016
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0015
183 Vascular endothelial growth factor A VEGFA 0.0014
1898 Cytochrome P450 1B1 CYP1B1 0.0011
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