Metrizamide

Identification

Name
Metrizamide
Accession Number
DB01578
Type
Small Molecule
Groups
Approved
Description

Metrizamide is a solute for density gradient centrifugation offering higher maximum solution density without the problems of increased viscosity. It is also used as a resorbable, non-ionic contrast medium.

Structure
Thumb
Synonyms
Not Available
External IDs
WIN 39103 / WIN-39103
International/Other Brands
Amipaque
Categories
UNII
RHH3W8F1CO
CAS number
31112-62-6
Weight
Average: 789.1
Monoisotopic: 788.8541
Chemical Formula
C18H22I3N3O8
InChI Key
DTZMSDADRKLCQE-RFMXWLSYSA-N
InChI
InChI=1S/C18H22I3N3O8/c1-6(27)22-14-11(19)10(12(20)15(13(14)21)24(3)7(2)28)18(32)23-8(4-25)16(30)17(31)9(29)5-26/h4,8-9,16-17,26,29-31H,5H2,1-3H3,(H,22,27)(H,23,32)/t8-,9+,16+,17+/m0/s1
IUPAC Name
3-[(1-hydroxyethylidene)amino]-2,4,6-triiodo-5-(N-methylacetamido)-N-[(2R,3R,4S,5R)-3,4,5,6-tetrahydroxy-1-oxohexan-2-yl]benzene-1-carboximidic acid
SMILES
[H][C@@](O)(CO)[C@@]([H])(O)[C@]([H])(O)[C@]([H])(C=O)N=C(O)C1=C(I)C(N=C(C)O)=C(I)C(N(C)C(C)=O)=C1I

Pharmacology

Indication

Metrizamide is used for lumbar, thoracic, cervical, and total columnar myelography to determine the presence of abnormalities in the spinal column, spinal canal, and central nervous system (CNS) as well as for cisternography by direct injection using standard radiologic techniques to visualize the basal cistern of the brain. For computerized tomography (CT) of the intracranial subarachnoid spaces and for ventriculography by direct injection using standard radiologic techniques to visualize the cerebral ventricles. Also used in pediatric angiocardiography to visualize lesions or malformations of the heart and obstructions or anomalies of the major thoracic vessels. Also used in adult peripheral arteriography to visualize specific regions of the vascular system and blood flow in such areas to help in the diagnosis and evaluation of neoplasms (known or suspected) or vascular diseases (congenital or acquired) that may cause changes in normal vascular anatomy or physiology. Metrizamide is also indicated in adults for intravenous digital arteriography of head and neck.

Pharmacodynamics

Metrizamide is a radiocontrast agent used to improve the contrast of internal body structures using different imaging techniques such as computed tomography scans (CT) or radiography (X-ray imaging).

Mechanism of action

Organic iodine compounds such as metrizamide block x-rays as they pass through the body, thereby allowing body structures containing iodine to be delineated in contrast to those structures that do not contain iodine. The degree of opacity produced by these compounds is directly proportional to the total amount (concentration and volume) of the iodinated contrast agent in the path of the x-rays. After intrathecal administration into the subarachnoid space, diffusion of metrizamide in the CSF allows the visualization of the subarachnoid spaces of the head and spinal canal. After intravascular administration, metrizamide makes opaque those vessels in its path of flow, allowing visualization of the internal structures until significant hemodilution occurs. Metrazamide also has some toxic effects which are thought to be due to its ability to inhibit glucose metabolism.

Absorption

Absorption from gastrointestinal tract is negligible following oral or rectal administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Non-ionic radiocontrast agents like metrizamide are cytotoxic to renal cells. The toxic effects include apoptosis, cellular energy failure, disruption of calcium homeostasis, and disturbance of tubular cell polarity, and are thought to be linked to oxidative stress.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Azuma H, Nomura S, Ikoma Y, Yokoyama M, Oshino N: A possible mechanism for the neural adverse reactions caused by metrizamide. Fortschr Geb Rontgenstrahlen Nuklearmed Erganzungsbd. 1989;128:134-42. [PubMed:2568781]
  2. Ekholm SE, Reece K, Coleman JR, Kido DK, Fischer HW: Metrizamide--a potential in vivo inhibitor of glucose metabolism. Radiology. 1983 Apr;147(1):119-21. [PubMed:6828715]
External Links
PubChem Compound
20056604
PubChem Substance
46506223
ChemSpider
16739315
ChEMBL
CHEMBL1200889
PharmGKB
PA164742936
Wikipedia
Metrizamide
ATC Codes
V08AB01 — Metrizamide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)223 dec °CPhysProp
water solubility5E+005 mg/L (at 25 °C)MERCK INDEX (1996)
logP-1.89HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0911 mg/mLALOGPS
logP-0.4ALOGPS
logP0.67ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)4.5ChemAxon
pKa (Strongest Basic)-0.18ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area183.48 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity143.32 m3·mol-1ChemAxon
Polarizability56.3 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9938
Blood Brain Barrier-0.9376
Caco-2 permeable-0.6755
P-glycoprotein substrateNon-substrate0.624
P-glycoprotein inhibitor INon-inhibitor0.6859
P-glycoprotein inhibitor IINon-inhibitor0.7024
Renal organic cation transporterNon-inhibitor0.9491
CYP450 2C9 substrateNon-substrate0.6989
CYP450 2D6 substrateNon-substrate0.8594
CYP450 3A4 substrateSubstrate0.5506
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8116
Ames testNon AMES toxic0.7685
CarcinogenicityNon-carcinogens0.8852
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.6272 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9949
hERG inhibition (predictor II)Non-inhibitor0.7864
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 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 acylaminobenzoic acid and derivatives. These are derivatives of amino benzoic acid derivatives where the amine group is N-acylated.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Acylaminobenzoic acid and derivatives
Alternative Parents
Hexoses / O-haloacetanilides / P-haloacetanilides / 2-halobenzoic acids and derivatives / 4-halobenzoic acids and derivatives / Benzamides / N-acetylarylamines / Benzoyl derivatives / Iodobenzenes / Aminosaccharides
show 13 more
Substituents
Acylaminobenzoic acid or derivatives / Hexose monosaccharide / O-haloacetanilide / P-haloacetanilide / Haloacetanilide / Acetanilide / 4-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / 2-halobenzoic acid or derivatives / N-acetylarylamine
show 33 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Drug created on August 29, 2007 08:52 / Updated on June 02, 2018 06:51