Gallamine triethiodide

Chemical Properties

White Solid

Originator

Flaxedil,Davis and Geck,US,1951

Uses

Muscle relaxant;M2 antagonist allosteric

Uses

Gallamine Triethiodide is used as a neuromuscular blocking agent, paralyzing locally during anesthetization.

Uses

Gallamine triethiodide has been used:

• as a relaxant for measuring spinal trigeminal nucleus recordings from single neurons.
• as an antagonist in neuroblastoma cells as M2 receptor
• to reduce eye movement during retinal surgery in rat

Manufacturing Process

12.6 grams of pyrogallol are dissolved in 100 cc of hot toluene. 14 grams of sodamide (85%)are added to the solution at about 100°C in 5 portions over a period of 15 minutes, with agitation. There are then added with agitation, over a period of 30 minutes, 100 cc of a toluene solution containing 474 grams of diethylaminochlorethane per liter of toluene.
The mixture is then heated for 1 hour, the toluene being refluxed, whereafter it is left to cool, 50 cc of water are added and, after decanting, the solution is again washed with two quantities of 50 cc of water. The toluene solution is dried over potassium carbonate and distilled in vacuo. There is thus obtained 28 grams of 1.2.3-tri-(β-diethylaminoethoxy)benzene, boiling at 206°C under 1 mm pressure.
20 grams of 1.2.3-tri-(β-diethylaminoethoxy)-benzene is heated for 5 hours under reflux on the water bath with 30 grams of ethyl iodide. The hot mixture is dissolved in 50 cc of water, filtered after addition of 2 grams of decolorizing black, evaporated to dryness on the water bath and recrystallized from 120 cc of alcohol. The product can be further recrystallized in mixtures of acetone and water.
The triethiodide of 1.2.3-tri-(β-diethylaminoethoxy)-benzene is thus obtained as white crystals which, after drying, have a rather indefinite melting point at about 152° to 153°C, (Maquenne block).

Therapeutic Function

Muscle relaxant

General Description

Gallamine triethiodide,[v-phenenyl-tris(oxyethylene)]tris[triethylammonium] triiodide(Flaxedil), is a skeletal muscle relaxant that works byblocking neuromuscular transmission in a manner similar tothat of d-tubocurarine (i.e., a nondepolarizing blockingagent). It does have some differences, however. It has astrong vagolytic effect and a persistent decrease in neuromuscularfunction after successive doses that cannot be overcome by cholinesterase inhibitors. Gallamine triethiodidealso has muscarinic antagonistic properties and bindswith greater affinity to the M2 receptors than to the M1 receptor.This latter characteristic may cause its strongvagolytic action.

Biochem/physiol Actions

Gallamine triethiodide has anti-muscarinic effect. It is a competitive antagonist for the muscarinic receptor. Gallamine is regarded as neuromuscular blocking agent.

Clinical Use

Gallamine Triethiodide is contraindicated in patients with myastheniagravis, and one should remember that its action is cumulative,as with curare. The antidote for gallamine triethiodideis neostigmine.

Safety Profile

Poison by ingestion, subcutaneous, intravenous, parenteral, intraduodenal, intraperitoneal, and intramuscular routes. Whenheated to decomposition it emits very toxic fumes of NH3, NOx, and Ií.

Synthesis

Gallamine, 1,2,3-tris-(2-triethylaminoethoxy)benzene triiodide, is synthesized from pyrogallol, the hydroxyl groups of which are esterified by 2-diethylaminoethylchloride in the presence of sodium amide. The resulting 1,2,3-tris-(2-triethylaminoethoxy) benzene is further alkylated at all three nitrogen atoms by ethyliodide, giving gallamine.