Identification

Name
Iobenguane
Accession Number
DB06704  (DB09497)
Type
Small Molecule
Groups
Approved, Investigational
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
Thumb
Synonyms
  • ((3-iodophenyl)methyl)guanidine
  • 3-iodobenzylguanidine
  • m-iodobenzylguanidine
  • Metaiodobenzylguanidine
  • mIBG
Product Ingredients
IngredientUNIICASInChI Key
Iobenguane I 123P2TH1XYZ8476924-93-1PDWUPXJEEYOOTR-IUAIQHPESA-N
Iobenguane I 131Q461L7AK4R77679-27-7PDWUPXJEEYOOTR-JRGAVVOBSA-N
Iobenguane sulfateS8I092246587862-25-7XNACDNPGABUBFR-UHFFFAOYSA-N
Iobenguane sulfate I 123Not Available139755-80-9Not applicable
Iobenguane sulfate I 131M575VKV19N149210-33-3Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AdreViewInjection2 mCi/1mLIntravenousMedi Physics Inc.2008-09-19Not applicableUs
AzedraInjection, solution15 mCi/1mLIntravenousProgenics Pharmaceuticals, Inc.2018-07-30Not applicableUs
Iobenguane Sulfate I 131 InjectionInjection2.3 mCi/2mLIntravenousPharmalucence, Inc.1994-03-252009-09-07Us
Categories
UNII
35MRW7B4AD
CAS number
80663-95-2
Weight
Average: 275.0896
Monoisotopic: 274.991940755
Chemical Formula
C8H10IN3
InChI Key
PDWUPXJEEYOOTR-UHFFFAOYSA-N
InChI
InChI=1S/C8H10IN3/c9-7-3-1-2-6(4-7)5-12-8(10)11/h1-4H,5H2,(H4,10,11,12)
IUPAC Name
2-[(3-iodophenyl)methyl]guanidine
SMILES
NC(N)=NCC1=CC(I)=CC=C1

Pharmacology

Indication

Detection of primary and metastatic pheochromocytoma or neuroblastoma

Pharmacodynamics

AdreView is a diagnostic radiopharmaceutical which contains a small quantity of iobenguane that is not expected to produce a pharmacodynamic effect. Patients with renal insufficiency may experience increased radiation exposure and impaired imaging results.

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.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

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%)

Half life

Physical half life = 13.2 hours

Clearance
Not Available
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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcebutololAcebutolol can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
AlaproclateAlaproclate may decrease effectiveness of Iobenguane as a diagnostic agent.
AmineptineAmineptine may decrease effectiveness of Iobenguane as a diagnostic agent.
AmitrazThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Amitraz.
AmitriptylineAmitriptyline can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmitriptylinoxideAmitriptylinoxide may decrease effectiveness of Iobenguane as a diagnostic agent.
Food Interactions
Not Available

References

General References
  1. Wafelman AR, Hoefnagel CA, Maes RA, Beijnen JH: Radioiodinated metaiodobenzylguanidine: a review of its biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry. Eur J Nucl Med. 1994 Jun;21(6):545-59. [PubMed:8082671]
External Links
KEGG Drug
D04559
PubChem Compound
60860
PubChem Substance
175427085
ChemSpider
54847
ChEBI
92769
ChEMBL
CHEMBL818
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Iobenguane
ATC Codes
V09IX02 — Iobenguane (131i)V09IX01 — Iobenguane (123i)V10XA02 — Iobenguane (131i)
FDA label
Download (187 KB)
MSDS
Download (93.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentCongestive Heart Failure (CHF)1
1, 2CompletedTreatmentParaganglioma / Pheochromocytomas1
1, 2Unknown StatusTreatmentNeuroblastomas1
2CompletedTreatmentNeuroblastomas1
2RecruitingTreatmentMIBG Avid Tumors1
3CompletedDiagnosticCongestive Heart Failure (CHF)2
3CompletedTreatmentNeoplasm Metastases / Neuroendocrine Tumors1
4CompletedDiagnosticHeart Failure, Unspecified / Ventricular Dysfunction, Left1
Not AvailableApproved for MarketingNot AvailableNeuroblastomas1
Not AvailableAvailableNot AvailableChildhood Metastatic Pheochromocytoma / Neuroblastomas / Paraganglioma1
Not AvailableAvailableNot AvailableNeuroblastomas1
Not AvailableAvailableNot AvailableNeuroblastomas / Pheochromocytomas1
Not AvailableAvailableNot AvailableParaganglioma / Pheochromocytomas1
Not AvailableCompletedTreatmentNeuroblastomas1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous2 mCi/1mL
Injection, solutionIntravenous15 mCi/1mL
InjectionIntravenous2.3 mCi/2mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)0°C MSDS
boiling point (°C)100°C MSDS
water solubilitySoluble MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0878 mg/mLALOGPS
logP1.53ALOGPS
logP1.64ChemAxon
logS-3.5ALOGPS
pKa (Strongest Basic)11.27ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area64.4 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity58.32 m3·mol-1ChemAxon
Polarizability21.93 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9057
Blood Brain Barrier+0.9003
Caco-2 permeable+0.5774
P-glycoprotein substrateNon-substrate0.6467
P-glycoprotein inhibitor INon-inhibitor0.9591
P-glycoprotein inhibitor IINon-inhibitor0.8833
Renal organic cation transporterInhibitor0.5244
CYP450 2C9 substrateNon-substrate0.8712
CYP450 2D6 substrateNon-substrate0.6132
CYP450 3A4 substrateNon-substrate0.7951
CYP450 1A2 substrateInhibitor0.9029
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9069
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9122
Ames testNon AMES toxic0.7308
CarcinogenicityNon-carcinogens0.9184
BiodegradationNot ready biodegradable0.9961
Rat acute toxicity2.9081 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9369
hERG inhibition (predictor II)Non-inhibitor0.9283
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as iodobenzenes. These are aromatic compounds containing one or more iodine atoms attached to a benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Iodobenzenes
Alternative Parents
Aryl iodides / Guanidines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Organopnictogen compounds / Organoiodides / Hydrocarbon derivatives
Substituents
Iodobenzene / Aryl iodide / Aryl halide / Guanidine / Organic 1,3-dipolar compound / Propargyl-type 1,3-dipolar organic compound / Carboximidamide / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
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
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. 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:14668769]

Drug created on May 15, 2010 18:19 / Updated on November 02, 2018 09:11