Iobenguane

Identification

Summary

Iobenguane is a radiopharmaceutical agent used for the diagnosis of primary and metastatic pheochromocytoma or neuroblastoma.

Brand Names
Azedra
Generic Name
Iobenguane
DrugBank Accession Number
DB06704
Background

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 275.0896
Monoisotopic: 274.991940755
Chemical Formula
C8H10IN3
Synonyms
  • ((3-iodophenyl)methyl)guanidine
  • 3-iodobenzylguanidine
  • m-iodobenzylguanidine
  • Metaiodobenzylguanidine
  • mIBG

Pharmacology

Indication

Detection of primary and metastatic pheochromocytoma or neuroblastoma

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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

Adverse Effects
Adverseeffects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololAcebutolol can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
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.
AmoxapineAmoxapine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmphetamineAmphetamine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
BenzphetamineBenzphetamine can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
BethanidineThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Bethanidine.
BromocriptineThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Bromocriptine.
ButriptylineButriptyline may decrease effectiveness of Iobenguane as a diagnostic agent.
CeliprololCeliprolol can cause a decrease in the absorption of Iobenguane resulting in a reduced serum concentration and potentially a decrease in efficacy.
Interactions
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Food Interactions
No interactions found.

Products

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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
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AdreViewInjection2 mCi/1mLIntravenousMedi-Physics Inc.2008-09-19Not applicableUS flag
AzedraInjection, solution15 mCi/1mLIntravenousProgenics Pharmaceuticals, Inc.2018-07-30Not applicableUS flag
Iobenguane Sulfate I 131 InjectionInjection2.3 mCi/2mLIntravenousPharmalucence, Inc.1994-03-252009-09-07US flag

Categories

ATC Codes
V09IX01 — Iobenguane (123i)V09IX02 — Iobenguane (131i)V10XA02 — Iobenguane (131i)
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aromatic homomonocyclic compound / Aryl halide / Aryl iodide / Carboximidamide / Guanidine / Hydrocarbon derivative / Iodobenzene / Organic 1,3-dipolar compound / Organic nitrogen compound / Organohalogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
35MRW7B4AD
CAS number
80663-95-2
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

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. [Article]
  2. FDA Approved Drug Products: AdreView (Iobenguane I 123 Injection) for Intravenous Use [Link]
  3. AZEDRA® (iobenguane I 131) FDA Label [Link]
KEGG Drug
D04559
PubChem Compound
60860
PubChem Substance
175427085
ChemSpider
54847
RxNav
14448
ChEBI
92769
ChEMBL
CHEMBL818
ZINC
ZINC000001538318
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Iobenguane
FDA label
Download (187 KB)
MSDS
Download (93.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticCardiomyopathy / Heart Failure1
4CompletedDiagnosticHeart Failure / Left Ventricular Dysfunction1
3CompletedDiagnosticCongestive Heart Failure (CHF)2
3CompletedDiagnosticCoronary Artery Disease (CAD) / Heart Failure1
3CompletedDiagnosticNeuroblastoma (NB) / Pheochromocytomas1
3CompletedTreatmentNeoplasm Metastases / Neuroendocrine Tumours (NETs)1
3TerminatedPreventionHeart Failure1
2CompletedTreatmentNeuroblastoma (NB)1
2RecruitingTreatmentMIBG Avid Tumors1
2RecruitingTreatmentNeoplasms / Neuroblastoma (NB) / Neuroectodermal Tumors1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous2 mCi/1mL
Injection, solutionIntravenous15 mCi/1mL
InjectionIntravenous2.3 mCi/2mL
Injection, solutionIntravenous
Injection, solution, concentrateIntravenous
SolutionIntravenous0.5 mg
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

Transporters

Kind
Protein
Organism
Humans
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. [Article]

Drug created on May 16, 2010 00:19 / Updated on January 07, 2021 03:11