3-[[(Dimethylamino)methylen]amino]-3-(2,4,6-triiodphenyl)propionsure

Insoluble

SLIGHTLY SOL IN ETHANOL; METHANOL /CALCIUM SALT/

VERY SOL IN CHLOROFORM /SODIUM SALT/

PRACTICALLY INSOL IN WATER; VERY SOL IN METHANOL, ETHANOL, CHLOROFORM, ACETONE, DILUTE SULFURIC ACID

168-169ºC

168-169 °C

DECOMPOSES @ 225 °C; ESTIMATED PK: 5-5.5

CRYSTALS; MP: 298-302 °C; SOL IN CHLOROFORM, DIMETHYLFORMAMIDE, HOT PROPYLENE GLYCOL; IN WATER @ 20 °C 0.1% /CALCIUM SALT/

VERY FREELY SOL IN WATER, METHANOL, ETHANOL; PRACTICALLY INSOL IN ACETONE, ETHER; SOLUBILITY IN DIMETHYLFORMAMIDE & DIMETHYL SULFOXIDE ABOUT 33 G/100 ML; IN DIMETHYLACETAMIDE ABOUT 66 G/100 ML; LEAFLETS FROM WATER + ACETONE; MP: 303-304 °C (DECOMP WITH EVOLUTION OF IODINE); BITTER LEAFLETS /SODIUM SALT/

ODORLESS; CHALKY, VERY BITTER TASTE /CALCIUM SALT/

ODORLESS /SODIUM SALT/

WHITE TO OFF-WHITE, CRYSTALLINE POWDER /CALCIUM & SODIUM SALTS/

Danger

H318 (100%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

P264+P265, P280, P305+P354+P338, and P317 (click each P-code to see the statement)

Aggregated GHS information provided per 24 reports by companies from 1 notifications to the ECHA C&L Inventory.

ONSET OF ACUTE IODIDE POISONING MAY OCCUR IMMEDIATELY OR SEVERAL HR AFTER ADMIN. ANGIOEDEMA IS OUTSTANDING SYMPTOM, & SWELLING OF LARYNX MAY LEAD TO SUFFOCATION. MULTIPLE CUTANEOUS HEMORRHAGES MAY BE PRESENT. ALSO MANIFESTATIONS OF SERUM-SICKNESS TYPE HYPERSENSITIVITY, SUCH AS FEVER, ARTHRALGIA, LYMPH NODE ENLARGEMENT, & EOSINOPHILIA, MAY APPEAR. THROMBOTIC THROMBOCYTOPENIC PURPURA & FATAL PERIARTERITIS NODOSA ATTRIBUTED TO HYPERSENSITIVITY TO IODIDE HAS BEEN DESCRIBED. /IODINE PREPN/

MEDIA USED FOR GI ROENTGENOGRAPHY & AGENTS ADMIN ORALLY MAY CAUSE NAUSEA, VOMITING, & DIARRHEA. ACUTE TUBULAR NECROSIS HAS BEEN REPORTED TO BE THE CONSEQUENCE OF INGESTION OF CERTAIN GALLBLADDER DYES. /IODINATED CONTRAST MEDIA/

THE WATER-SOLUBLE COMPOUNDS ARE RESPONSIBLE FOR 2 TYPES OF SEVERE REACTIONS: (1) INFREQUENTLY...SEVERE RESPIRATORY DIFFICULTY WITH WHEEZING, BRONCHIAL & LARYNGEAL SPASM, SWELLING OF LIPS & EYELIDS, & GIANT URTICARIA. ... (2) SOMEWHAT MORE FREQUENT IS...CARDIOVASCULAR COLLAPSE IN WHICH THERE IS FALL IN BLOOD PRESSURE, TACHYCARDIA, DYSPNEA, & CONFUSION & CYANOSIS PROGRESSING TO UNCONSCIOUSNESS. /WATER-SOLUBLE IODINATED CONTRAST MEDIA/

UNTOWARD EFFECTS REPORTED INCL ABDOMINAL CRAMPING, DIARRHEA, NAUSEA, VOMITING, DYSURIA, URTICARIA, HEADACHE, HEARTBURN, & EPIGASTRIC PAIN. ALTHOUGH RARE, HYPOTENSION & CIRCULATORY COLLAPSE HAVE BEEN REPORTED. /IPODATE CALCIUM & SODIUM/

The thyroid effects of iopodic acid are related to the blocking of the more potent form of the thyroid hormone. It also blocks thyroid hormone release and it can interfere with its synthesis in some patients. The effects of iopopdic acid on some diseases, such as Graves disease, have been shown not to be as effective and to present a relapse after discontinuation. The effects of iopodic acid on thyroid has been proven to produce an inactivation of approximately 80% of the type II deiodinase in pituitary and cerebral cortex.

For cholecystography, iopodic acid blocks the X-rays as they pass through the body which allows delineating the body structures that do not contain this compound. The use of iopodic acid in hyperthyroidism is related to the inhibition of 5'-monodeiodinase type I and II; this will later impair the extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3).

IPODATE /ORAGRAFIN/...GIVEN ONCE DAILY CAUSES RAPID DECLINE IN SERUM T3 & T4, INCREASES RT3, & APPEARS TO BE MORE POTENT THAN PTU IN INHIBITING EXTRATHYROIDAL CONVERSION OF T4 TO T3. ANOTHER MECHANISM PROBABLY INVOLVES THE SLOWER INHIBITION OF THYROID HORMONE SECRETION CAUSED BY RELEASE OF IODINE AFTER METABOLISM OF IPODATE. THE USE OF IPODATE & SIMILAR AGENTS IS INVESTIGATIONAL BUT APPEARS PROMISING FOR SHORT-TERM EARLY TREATMENT OF HYPERTHYROIDISM OR AS AN ADJUNCT TO THIOAMIDE DRUGS. /IPODATE SALTS/

THE INGESTION BY NORMAL SUBJECTS OF 3 G OF SODIUM IPODATE RESULTED IN DECREASES OF SERUM TOTAL & FREE T3 TO A NADIR ON DAY 4 WHICH AVERAGED 43% & 40%, RESPECTIVELY, BELOW INITIAL MEAN VALUES. TOTAL & FREE RT3 INCREASED MARKEDLY TO PEAK ON DAY 3, 244% & 189%, RESPECTIVELY, ABOVE INITAL MEAN VALUES. CHANGES OBSERVED AFTER ADMINISTRATION OF IPODATE WERE CONSISTENT WITH AN EFFECT ON THE PERIPHERAL METABOLISM OF T4.

IPODATE INHIBITED BINDING OF (125)I-LABELED T3 IN VITRO. IT PRODUCED A 50% INHIBITION OF BINDING AT 1.2X10-4 MOLAR. WHEN GIVEN ORALLY IN ACTIVE IN VIVO EXPERIMENTS, IPODATE DID NOT DIMINISH BINDING TO LIVER NUCLEAR RECEPTORS, BUT APPEARED TO INHIBIT IN VIVO METABOLISM OF LABELED T3.

IPODATE IS AN EFFECTIVE, COMPETITIVE IN VITRO INHIBITOR OF (125)I-LABELED T3 BINDING TO RAT HEPATIC NUCLEI RECEPTORS. T3 RECEPTOR BINDING INHIBITION ALSO OCCURRED WHEN IPODATE WAS GIVEN IV TO RATS.

3,3'-DIIODOTHYRONINE (3,3'-T2) SECRETION FROM PERFUSED CANINE THYROID ISOLATED IN SITU, WAS INHIBITED BY IPODATE (10-5 MOLES).

The lipophilicity of ipodate is sufficient for passage through the gastrointestinal mucosa. After ingestion, iopodic acid is promptly absorbed by passive diffusion in the small intestinal mucosa. The presence of bile salts in the duodenum is essential for its diffusion through the intestine wall and a high-fat diet is important in order to increase the absorption effectivity. The maximum effect is showed to be attained 5 hours after the initial dosage and the effect were retained for more than 60 hours.

The metabolism products of ipodate are readily excreted into the bile, follow the bile flow to fill up the gallbladder and then excreted by the biliary system in the feces. This mode of excretion accounts for 65% of the eliminated dose whereas the kidneys are responsible for the remaining 35% of the elimination.

...RAPIDLY ABSORBED FROM GI TRACT & EXCRETED IN BILE... /IPODATE CALCIUM/

...SOMEWHAT LESS RAPIDLY ABSORBED FROM GI TRACT.../WHEN COMPARED WITH IPODATE CALCIUM/. /IPODATE SODIUM/

PRIEWE, POLJAK, BER 93, 2347 (1960).

BY PRECIPITATION USING AQUEOUS SOLN OF SODIUM IPODATE & CALCIUM CHLORIDE. THE CRUDE PRECIPITATE IS RECRYSTALLIZED FROM A SUITABLE SOLVENT SUCH AS AQUEOUS DIMETHYLFORMAMIDE. /IPODATE CALCIUM/

3-AMINO-2,4,6-TRIIODOHYDROCINNAMIC ACID IS CONDENSED WITH N,N-DIMETHYLFORMAMIDE WITH THE AID OF IODOMETHANESULFONYL CHLORIDE. THE REACTION MIXTURE IS THEN POURED INTO ICE WATER WHICH PRECIPITATES 3[[(DIMETHYLAMINO)METHYLENE]AMINO]-2,4,6-TRIIODOHYDROCINNAMIC ACID. NEUTRALIZATION OF ACID WITH SODIUM HYDROXIDE YIELDS SODIUM SALT... /IPODATE SODIUM/

SODIUM IPODATE, BILOPTIN, ORAGRAFIN-SODIUM. /SODIUM IPODATE/; CALCIUM IPODATE, SOLUBILOPTIN, ORAGRAFIN-CALCIUM. /CALCIUM IPODATE/.

/IPODATE CALCIUM/...CONTAINS 61.7% IODINE... /IPODATE SODIUM/...CONTAINS 61.4% IODINE... /IPODATE CALCIUM & SODIUM/