Neuromuscular Blocking Agents

Abstract

Abstract The preparation of two further NSN-tris-ethonium compounds, 9-ethyl-9-thioniaheptadecylenebis(triethylammonium) triiodide (dioctasulphonium triethiodide; DOSE) and 11-ethyl-11-thioniaheneicosylenebis(triethylammonium) triiodide (didecasulphonium triethiodide; DDSE) is described. The bis-quaternary compound 7-dioxothiatridecylenebis(triethylammonium iodide), and the NNN-tris-quaternary compounds 7:7-diethyl-7-azoniatridecylenebis (triethylammonium) triiodide (dihexazonium triethiodide; DHAE), 9:9-diethyl-9-azoniaheptadecylenebis(triethylammonium triiodide (dioctazonium triethiodide; DOAE) and 11:11-diethyl-11-azoniahenicosylenebis(triethylammonium) triiodide (didecazonium triethiodide; DDAE) have also been synthesised. All the compounds possess neuromuscular blocking activity in the gastrocnemius muscle-sciatic nerve preparation of the cat, the phrenic nerve-diaphragm preparation of the rat and kitten and as measured by the rabbit head drop and mouse paralysis methods. Dihexazonium triethiodide and the sulphone 7-dioxathiatridecylenebis(triethylammonium iodide) (dihexone) show tubocurarine-like activity; dioctasulphonium triethiodide and dioctazonium triethiodide were predominantly tubocurarine-like but had some transitional properties, whilst didecasulphonium triethiodide and didecazonium triethiodide resembled decamethonium. Dihexazonium triethiodide was about equipotent with tubocurarine on the cat. Marked species variations in potency were observed. Theoretical implications are discussed.