ISOPROPAMIDE IODIDE

Originator

Darbid,SKF,US,1957

The Uses of ISOPROPAMIDE IODIDE

Isopropamide Iodide acts as an anticholinergic compound with inhibitory activity. Also acts as a muscarinic receptor antagonist which can be applied to treatment of diseases affecting cognition including Alzheimer’s disease.

The Uses of ISOPROPAMIDE IODIDE

Isopropamide inhibits muscarinic action of acetylcholine on postganglionic parasympathetic effector regions. It is used for treating stomach ulcers and inflamed intestine.

Definition

ChEBI: Isopropamide iodide is a diarylmethane.

Manufacturing Process

γ-Diisopropylamino-α,α-diphenylbutyronitrile (60 g) was added in several portions to a mixture of sulfuric acid (150 ml) and water (15 ml) and the solution was heated 3% hours on the steam bath and then poured on ice and made basic with NH4OH. The γ-diisopropylamino-α,α-diphenylbutyramide precipitated as a solid, which was taken up in methylene chloride from an aqueous slurry. The methylene chloride was separated and dried by filtering through anhydrous K2CO3. The solvent was removed by distillation, leaving the amide which was crystallized from Skellysolve B five times and found then to have MP 87.0° to 88.5°C.
γ-Diisopropylamino-α,α-diphenylbutyramide in propanol was refluxed 4 hours in the presence of excess methyl iodide. Upon dilution of the solution with ethyl acetate (100 ml per 50 ml isopropyl alcohol) and cooling γ- diisopropylamino-α,α-diphenylbutyramide methiodide precipitated, was collected by filtration and recrystallized (9.0 g) by dissolving in a hot mixtureof 100 ml isopropyl alcohol and 10 ml methanol and then diluting with 90 ml Skellysolve B, to give 8.3 g recrystallized product, MP 182° to 184°C.

brand name

Darbid (GlaxoSmithKline).

Therapeutic Function

Spasmolytic

General Description

Isopropamide iodide, 3-carbamoyl-3,3-diphenylpropyl)diisopropylmethylammoniumiodide (Darbid), occurs as a bitter, white to pale yellow, crystallinepowder that is only sparingly soluble in water butfreely soluble in chloroform and alcohol.
This drug, introduced in 1957, is a potent anticholinergic,producing atropine-like effects peripherally. Even with itsquaternary nature, it does not cause sympathetic blockade atthe ganglionic level except at high dosages. Its principal distinguishingfeature is its long duration of action. A singledose can provide antispasmodic and antisecretory effects foras long as 12 hours.

Clinical Use

ISOPROPAMIDE IODIDE is used as adjunctive therapy in the treatment of pepticulcer and other conditions of the GI tract associated withhypermotility and hyperacidity. It has the usual side effectsof anticholinergics (dryness of mouth, mydriasis, difficulturination) and is contraindicated in glaucoma, prostatic hypertrophy,etc.

Synthesis

Isopropamide, (3-carbamoyl-3,3-diphenylpropyl)di-iso-propylmethyl ammonium iodide (14.1.25), is synthesized by alkylating diphenylacetonitrile with di-isopropylaminoethylchloride in the presence of sodium amide, and the subsequent hydrolysis of the nitrile group of the resulting compound (14.1.23) to an amide group (14.1.24). Alkylation of this compound with methyliodide gives isopropamide (14.1.25) [19¨C22].