EFFECTS OF , -BIS-(DIMETHYLAMMONIUMACETALDEHYDE DIETHYLACETAL) -p , p-DIACETYLBIPHENYL BROMIDE (DMAE) ON NEUROMUSCULAR TRANSMISSION

¹ Department of Pharmacology, University of Iowa, College of Medicine, Iowa City, Iowa

, -Bis-(dimethylammoniumacetaldehyde diethylacetal)-p, -diacetylbiphenyl bromide (DMAE) has been found to block neuromuscular transmission at rabbit sciatic nerve-gastrocnemius muscle. During the early phase of blockade, the effect of DMAE was augmented by choline, suggesting that there is no hemicholinium (HC-3)-like blockade of acetylcholine (ACh) synthesis. During the late phase of neuromuscular blockade, however, the DMAE blockade was reversed by choline but not by decamethonium nor by d-tubocurarine. Neostigmine antagonized the effect of DMAE when the dose of DMAE was low (0.2 mg/kg) but not when the dose was high (2 mg/kg). These results indicate that DMAE might be slowly converted into HC-3 in the body to block the ACh synthesis during the late phase. The ED50's of DMAE were fairly close to those of HC-3, which might also indicate the conversion of DMAE to HC-3. DMAE appears not to be a depolarizing agent since 1) it blocked neuromuscular transmission without initial facilitation; 2) its neuromuscular blockade was unaffected or partially antagonized by neostigmine; 3) it did not contract frog rectus abdominis muscle, guinea-pig ileum and baby chicken biventer cervicis muscle; and 4) it blocked ACh and nicotine responses on frog rectus abdominis muscle. However, the nondepolarizing blockade of DMAE was not a curare-like effect because there was no parallel shift of the dose-response curves of ACh on frog rectus abdominis muscle by DMAE.