Antagonism by beta-eudesmol of neostigmine-induced neuromuscular failure in mouse diaphragms.
beta-Eudesmol, a sesquiterpenol extracted from a Chinese herb, Atractylodes lancea, at 10-80 microM, did not affect muscle action potentials, miniature and evoked endplate potentials and acetylcholine-induced depolarization in the presence or absence of neostigmine in mouse phrenic nerve-diaphragms. However, the tetanic fade, muscle fasciculation and twitch potentiation induced by neostigmine were effectively antagonized by 20 microM beta-eudesmol. When trains of pulses were applied to the nerve in the presence of neostigmine, beta-eudesmol reduced the incidence of explosive depolarization of the endplate from 95% to 35-67% of junctions, and shortened the duration when it occurred. Moreover, both the maximal and steady-state depolarizations during repetitive stimulation were reduced while the amplitudes of steady-state endplate potentials were increased. The results suggest that beta-eudesmol antagonized neostigmine-induced neuromuscular failure mainly by a presynaptic action to depress the regenerative release of acetylcholine during repetitive stimulation. The mechanism of antagonism is obviously not tubocurarine-like and it is unrelated to desensitization of acetylcholine channels.
Chiou
L C
LC
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Chang
C C
CC
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation*; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D009466:Neuromuscular Blocking Agents; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; D009388:Neostigmine; C051082:beta-eudesmol; D000109:Acetylcholine