Structural components of beta-eudesmol essential for its potentiating effect on succinylcholine-induced neuromuscular blockade in mice.
beta-Eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea rhizoma, potentiates the neuromuscular blocking effect of succinylcholine (SuCh). The potentiating effect is greater in diabetic muscles than in normal ones. To identify the structural components of beta-eudesmol contributing to this action, we examined the potentiating effect of newly synthesized tertiary alcohols related to beta-eudesmol in phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. Potentiating effects were exhibited by cyclohexylidene derivatives but not by cyclohexanone or cyclohexanol derivatives. The compound 2-(3-hydroxy-3-methylbutyl)cyclohexylidene exhibited a potentiating effect, but 3-(3-hydroxy-3-methylbutyl)cyclohexylidene did not. These results indicate that both the presence of an exo-methylene attached to a cyclohexane ring and the distance between the exo-methylene and the hydroxy group in beta-eudesmol are involved in the potentiating effect on SuCh-induced neuromuscular blockade.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
M
M
Kimura
K
K
Tanaka
Y
Y
Takamura
H
H
Nojima
I
I
Kimura
S
S
Yano
M
M
Tanaka
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003964:Diaphragm / Q000187:drug effects / Q000294:innervation; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000187:drug effects; D045787:Sesquiterpenes, Eudesmane; D013329:Structure-Activity Relationship; D013390:Succinylcholine / Q000494:pharmacology*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D009466:Neuromuscular Blocking Agents; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; C051082:beta-eudesmol; D013390:Succinylcholine