Abstract
A study was undertaken of the relation between autonomic effects and chemical structure among a cries of compounds related to McN-A-343, 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride. A shift of the chlorine atom from position 3 to position 4 produces a 3-fold enhancement of ganglionic stimulant activity qualitatively similar to that induced by McN-A-343, i.e., it is readily antagonized by atropine. Shift of the chlorine atom to position 2 causes a decrease to [unknown] the activity of McN-A-343. m-Trifluoro or 2.5-dichloro substitution also reduces activity, as does saturation of the acetylenic group to an ethylenic group. The fully saturated material is devoid of ganglionic stimulant effects, producing instead depolarizing-type neuromuscular blockade; this substance is approximately [unknown] to [unknown] as active as decamethonium. Only the quaternary ammonium compounds display autonomic effects of consequence. The triethylammonium substituted analog displays a mixture of short-acting ganglionic blockade (hexamethoniumlike) and atropine-like effects. Removal of the chlorophenyl portion of this molecule results in the formation of compounds which display marked cholinomimetic activity. These range in potency from [unknown] to ½ times that of acetylcholine.
Footnotes
- Received March 3, 1966.
- Accepted December 9, 1966.
- © 1967 by The Williams & Wilkins Company
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|