DT-Web

DB00830 - Phenmetrazine


Identification
Name Phenmetrazine
Accession Number DB00830 (APRD00262)
Type small molecule
Description A sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 177.2429
Groups illicit
Monoisotopic Weight 177.115364107
Pharmacology
Indication Used as an anorectic in the treatment of obesity.
Mechanism of action Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.
Absorption Readily absorbed from the gastro-intestinal tract and buccal mucosa.
Protein binding Not Available
Biotransformation Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation.
Route of elimination Not Available
Toxicity Adult monkeys have an LD50 of 15 to 20 mg/kg, whereas for young monkeys the LD50 is only 5 mg/kg. Symptoms of overdose include acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension, and cardiovascular collapse. Whilst some patients show signs of toxicity at blood concentrations of 20 µg/L, chronic abusers of amphetamine have been known to have blood concentration of up to 3000 µg/L.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Chlorpromazine Decreased anorexic effect, may increase psychotic symptoms
Fluphenazine Decreased anorexic effect, may increase psychotic symptoms
Guanethidine Phenmetrazine 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
Perphenazine Decreased anorexic effect, may increase psychotic symptoms
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
Trifluoperazine Decreased anorexic effect, may increase psychotic symptoms
Food Interactions Not Available

Targets


Sodium-dependent noradrenaline transporter
Name Sodium-dependent noradrenaline transporter
Gene Name SLC6A2
Pharmacological action yes
Actions inhibitor
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
  • Rothman RB, Katsnelson M, Vu N, Partilla JS, Dersch CM, Blough BE, Baumann MH: Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7. - Pubmed
  • Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. - Pubmed
DTHybrid score 0.4483
Sodium-dependent dopamine transporter
Name Sodium-dependent dopamine transporter
Gene Name SLC6A3
Pharmacological action yes
Actions inhibitor
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
  • Rothman RB, Katsnelson M, Vu N, Partilla JS, Dersch CM, Blough BE, Baumann MH: Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7. - Pubmed
  • Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. - Pubmed
DTHybrid score 0.455

Predictions


Id Partner name Gene Name Score
824 Sodium-dependent serotonin transporter SLC6A4 0.2074
4119 Cytochrome P450 2D6 CYP2D6 0.1066
556 Alpha-1A adrenergic receptor ADRA1A 0.0677
131 Synaptic vesicular amine transporter SLC18A2 0.0668
4512 Cytochrome P450 3A4 CYP3A4 0.0632
3941 Amine oxidase [flavin-containing] A MAOA 0.0498
632 Alpha-1B adrenergic receptor ADRA1B 0.0474
492 Histamine H1 receptor HRH1 0.0458
3939 Amine oxidase [flavin-containing] B MAOB 0.043
318 Alpha-2A adrenergic receptor ADRA2A 0.0357
6016 Cytochrome P450 2C19 CYP2C19 0.035
4200 Cytochrome P450 1A2 CYP1A2 0.0334
1588 Multidrug resistance protein 1 ABCB1 0.033
502 5-hydroxytryptamine 2A receptor HTR2A 0.0309
6030 Cytochrome P450 2B6 CYP2B6 0.0285
4757 Cytochrome P450 2C9 CYP2C9 0.0281
1636 Trace amine-associated receptor 1 TAAR1 0.028
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0268
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0219
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0199
629 Alpha-2B adrenergic receptor ADRA2B 0.0187
590 5-hydroxytryptamine 2C receptor HTR2C 0.0186
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.017
193 Beta-1 adrenergic receptor ADRB1 0.0147
341 5-hydroxytryptamine 3 receptor HTR3A 0.0145
766 Beta-2 adrenergic receptor ADRB2 0.0144
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0142
3923 Cholinesterase BCHE 0.0136
4118 Cytochrome P450 3A5 CYP3A5 0.0135
378 Alpha-2C adrenergic receptor ADRA2C 0.0135
6147 Solute carrier family 22 member 3 SLC22A3 0.0134
6144 Solute carrier family 22 member 2 SLC22A2 0.0124
436 5-hydroxytryptamine 2B receptor HTR2B 0.012
6013 Cytochrome P450 2E1 CYP2E1 0.0113
118 Organic cation/carnitine transporter 2 SLC22A5 0.011
1517 Beta-3 adrenergic receptor ADRB3 0.0109
6107 Cytochrome P450 3A7 CYP3A7 0.0105
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0105
1757 Myeloperoxidase MPO 0.0103
4924 Cytochrome P450 2C8 CYP2C8 0.0099
1656 CYP2B protein CYP2B 0.0097
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.0095
320 5-hydroxytryptamine 1A receptor HTR1A 0.0093
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0092
789 Alpha-1D adrenergic receptor ADRA1D 0.0091
831 D(2) dopamine receptor DRD2 0.0089
6145 Solute carrier family 22 member 1 SLC22A1 0.0088
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0084
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0082
5718 Cytochrome P450 2A6 CYP2A6 0.0082
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0073
23 D(1A) dopamine receptor DRD1 0.007
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0066
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0065
6164 POU domain, class 5, transcription factor 1 POU5F1 0.006
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0057
4120 NADPH--cytochrome P450 reductase POR 0.0057
6432 Transporter snf 0.0053
467 Delta-type opioid receptor OPRD1 0.005
696 Kappa-type opioid receptor OPRK1 0.005
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0048
6024 Cytochrome P450 1A1 CYP1A1 0.0048
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0046
474 Acetylcholinesterase ACHE 0.0045
2981 Phospholipase A2, membrane associated PLA2G2A 0.0044
828 Phenylalanine-4-hydroxylase PAH 0.0043
3109 Phenylalanine-4-hydroxylase phhA 0.0043
6182 Cytochrome P450 2J2 CYP2J2 0.0041
847 Mu-type opioid receptor OPRM1 0.004
482 Glycine receptor subunit alpha-1 GLRA1 0.004
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0039
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
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0033
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0029
587 Serum albumin ALB 0.0027
153 Dopamine beta-hydroxylase DBH 0.0025
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0025
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0025
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0024
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0023
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0022
904 Glutathione S-transferase P GSTP1 0.002
3810 Catechol O-methyltransferase COMT 0.002
163 D(1B) dopamine receptor DRD5 0.0019
725 5-hydroxytryptamine 1D receptor HTR1D 0.0019
885 5-hydroxytryptamine 1B receptor HTR1B 0.0019
432 D(4) dopamine receptor DRD4 0.0018
638 D(3) dopamine receptor DRD3 0.0018
6151 Monocarboxylate transporter 10 SLC16A10 0.0018
6106 Cytochrome P450 2C18 CYP2C18 0.0017
1360 Sphingomyelin phosphodiesterase SMPD1 0.0017
833 Organic cation/carnitine transporter 1 SLC22A4 0.0017
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0015
1618 High affinity nerve growth factor receptor NTRK1 0.0012
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0011
124 Histamine H2 receptor HRH2 0.0011
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0009
20 Prostaglandin G/H synthase 1 PTGS1 0.0009
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