DT-Web

DB06704 - Iobenguane


Identification
Name Iobenguane
Accession Number DB06704
Type small molecule
Description Synthetic guanethidine derivative that locates phaeochromocytomas and neuroblastomas. The radioisotope used can either be iodine-123 for imaging or iodine-131 for destruction of tissues that metabolize noradrenaline. Iodine 123 is a cyclotron-produced radionuclide that decays to Te 123 by electron capture. Images are produced by a I123 MIBG scintigraphy. FDA approved on September 19, 2008.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 275.0896
Groups approved
Monoisotopic Weight 274.991940755
Pharmacology
Indication Detection of primary and metastatic pheochromocytoma or neuroblastoma
Mechanism of action Structure of iobenguane is similar to noradrenaline so it can be taken up by adrenergic tissue in the adrenal medulla, liver, heart, and spleen. Once taken up by noradrenaline transporters in the adrenergic nerve terminals, it is stored in the presynaptic storage vesicles. The radioactive iodine component is responsible for its imaging properties.
Absorption Iobenguane rapidly clears from the blood and is highly retained in adrenergic tissues.
Protein binding Not Available
Biotransformation Less than 10% of the dose is metabolized into m-iodohippuric acid (MIHA). However the mechanism in which this metabolite is produced is unknown.
Route of elimination Renally excreted unchanged (70%-90%) via glomerular filtration; Fecal (<1%)
Toxicity Oral mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50=980 mg/kg. The most common adverse reactions, dizziness, rash, pruritis, flushing, headache, and injection site hemorrhage occurred in < 1.3% of patients.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Amitriptyline May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
Cocaine Sympathomimetic that increase chances of producing a false negative imaging result
Ephedrine Sympathomimetic that increase chances of producing a false negative imaging result
Imipramine May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it inhibits noradrenaline transporter function
Labetalol May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it depletes or inhibit reuptake of noradrenaline stores
Milnacipran Milnacipran decreases the effects of Iobenguane thus increases the risk of producing a false-negative result. May discontinue milnacipran for at least 5 half-live.
Phenylephrine Sympathomimetic that increase chances of producing a false negative imaging result
Phenylpropanolamine Sympathomimetic that increase chances of producing a false negative imaging result
Pseudoephedrine Sympathomimetic that increase chances of producing a false negative imaging result
Reserpine May diminish the therapeutic effect and increase chances of producing a false negative imaging result of Iobenguane as it depletes or inhibit reuptake of noradrenaline stores
Food Interactions Not Available

Transporters


Sodium-dependent noradrenaline transporter
Name Sodium-dependent noradrenaline transporter
Gene Name SLC6A2
Actions substrate
References
  • Gerson MC, Wagoner LE, McGuire N, Liggett SB: Activity of the uptake-1 norepinephrine transporter as measured by I-123 MIBG in heart failure patients with a loss-of-function polymorphism of the presynaptic alpha2C-adrenergic receptor. J Nucl Cardiol. 2003 Nov-Dec;10(6):583-9. - Pubmed
DTHybrid score 0.315

Predictions


Id Partner name Gene Name Score
824 Sodium-dependent serotonin transporter SLC6A4 0.1183
713 Sodium-dependent dopamine transporter SLC6A3 0.1045
4119 Cytochrome P450 2D6 CYP2D6 0.0563
556 Alpha-1A adrenergic receptor ADRA1A 0.0444
4512 Cytochrome P450 3A4 CYP3A4 0.0398
1588 Multidrug resistance protein 1 ABCB1 0.0249
131 Synaptic vesicular amine transporter SLC18A2 0.0246
632 Alpha-1B adrenergic receptor ADRA1B 0.0194
502 5-hydroxytryptamine 2A receptor HTR2A 0.0192
318 Alpha-2A adrenergic receptor ADRA2A 0.0177
3941 Amine oxidase [flavin-containing] A MAOA 0.0173
4200 Cytochrome P450 1A2 CYP1A2 0.017
6016 Cytochrome P450 2C19 CYP2C19 0.0168
492 Histamine H1 receptor HRH1 0.0166
3939 Amine oxidase [flavin-containing] B MAOB 0.0146
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0142
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0142
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0141
4757 Cytochrome P450 2C9 CYP2C9 0.0133
6030 Cytochrome P450 2B6 CYP2B6 0.0132
590 5-hydroxytryptamine 2C receptor HTR2C 0.0119
629 Alpha-2B adrenergic receptor ADRA2B 0.0114
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0092
789 Alpha-1D adrenergic receptor ADRA1D 0.0091
1636 Trace amine-associated receptor 1 TAAR1 0.0088
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0086
193 Beta-1 adrenergic receptor ADRB1 0.0085
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0084
766 Beta-2 adrenergic receptor ADRB2 0.0083
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0082
378 Alpha-2C adrenergic receptor ADRA2C 0.0081
6013 Cytochrome P450 2E1 CYP2E1 0.0074
1517 Beta-3 adrenergic receptor ADRB3 0.0072
436 5-hydroxytryptamine 2B receptor HTR2B 0.0068
4924 Cytochrome P450 2C8 CYP2C8 0.0064
6144 Solute carrier family 22 member 2 SLC22A2 0.0061
831 D(2) dopamine receptor DRD2 0.0056
320 5-hydroxytryptamine 1A receptor HTR1A 0.0054
6432 Transporter snf 0.0053
4118 Cytochrome P450 3A5 CYP3A5 0.0052
467 Delta-type opioid receptor OPRD1 0.005
696 Kappa-type opioid receptor OPRK1 0.005
6147 Solute carrier family 22 member 3 SLC22A3 0.005
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0048
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0048
6107 Cytochrome P450 3A7 CYP3A7 0.0048
6024 Cytochrome P450 1A1 CYP1A1 0.0048
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0046
6145 Solute carrier family 22 member 1 SLC22A1 0.0046
474 Acetylcholinesterase ACHE 0.0045
2981 Phospholipase A2, membrane associated PLA2G2A 0.0044
1757 Myeloperoxidase MPO 0.0044
828 Phenylalanine-4-hydroxylase PAH 0.0043
3109 Phenylalanine-4-hydroxylase phhA 0.0043
3923 Cholinesterase BCHE 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
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0036
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0036
118 Organic cation/carnitine transporter 2 SLC22A5 0.0036
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0036
23 D(1A) dopamine receptor DRD1 0.0036
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0033
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0029
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0028
587 Serum albumin ALB 0.0027
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0027
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0027
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
341 5-hydroxytryptamine 3 receptor HTR3A 0.0024
5718 Cytochrome P450 2A6 CYP2A6 0.0024
1656 CYP2B protein CYP2B 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
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0019
725 5-hydroxytryptamine 1D receptor HTR1D 0.0019
885 5-hydroxytryptamine 1B receptor HTR1B 0.0019
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
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0016
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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