Studies on action mechanisms of a possible false cholinergic transmitter, (2-hydroxyethyl) methyldiethylammonium

(2-Hydroxyethyl) methyldiethylammonium (DEC; Diethylcholine) was found to inhibit cholinergic fibers slowly, both in skeletal muscle (ED₅₀: 2.25 × 10^?5 M in chick biventer cervicis and 42 mg/kg in rat sciatic-gastrocnemius) and in smooth muscle preparations (ED₅₀: 7.7 × 10^?4 M in transmurally stimulated guinea-pig ileum) without having any effect on dose-response curves of acetylcholine to contract chick biventer cervicis, frog rectus abdominis and guinea-pig ileum. These results indicate that DEC acts at the prejunctional nerve fibers, but not at the postjunctional cholinergic receptor sites. DEC was acetylated efficiently both by choline acetyltransferase and by minced rat brain, suggesting that it can be acetylated to acetyl-DEC in the nerve ending. Acetyl-DEC was found to block acetylcholine actions competitively both in smooth and in skeletal muscle preparations (1 × 10^?3 ? 1 × 10^?2M) indicating that the acetylated product of DEC can serve as an antagonist at the cholinergic receptor site. It is therefore concluded that DEC is a false cholinergic transmitter.