Potentiating effects of beta-eudesmol-related cyclohexylidene derivatives on succinylcholine-induced neuromuscular block in isolated phrenic nerve-diaphragm muscles of normal and alloxan-diabetic mice.
beta-Eudesmol, a sesquiterpenoid alcohol contained in Atractylodes lancea, potentiates succinylcholine (SuCh)-induced neuromuscular blockade. The potentiating effect is greater in diabetic muscles than in normal ones. As a ligand for affinity chromatography to study the potentiating mechanism, we designed and synthesized newly beta-eudesmol-related cyclohexylidene derivatives (2-(3-hydroxy-3-methylbutyl)cyclohexylidene; KTE-13, 2-(3-hydroxy-3-methylbutyl)-4-cyclohexylidene carboxylic acid; KTE-32 and 4-tert-butoxycarbonyl-2-(3-hydroxy-3-methylbutyl) cyclohexylidene; KTE-33). We examined the potentiating effects of those compounds in phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. KTE-33 (100 microM) potentiated more greatly SuCh-induced neuromuscular blockade in diabetic muscles than in normal ones (the potentiating ratios in normal and diabetic muscles were 6.7 and 10.6, respectively), while KTE-13 (100 microM) and -32 (200 microM) potentiated weakly. These results suggest that the ester group in KTE-33 rather than a carboxyl group in KTE-32 is important in inducing the potentiation of SuCh-induced neuromuscular blockade in diabetic state.
Kimura
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Diwan
P V
PV
Yanagi
S
S
Kon-no
Y
Y
Nojima
H
H
Kimura
I
I
D000818:Animals; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003964:Diaphragm / Q000187:drug effects* / Q000294:innervation*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects*; D045787:Sesquiterpenes, Eudesmane; D013268:Stimulation, Chemical; D013390:Succinylcholine / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*
C095916:2-(3-hydroxy-3-methylbutyl)-4-cyclohexylidine carboxylic acid; C095915:2-(3-hydroxy-3-methylbutyl)cyclohexylidene; D003510:Cyclohexanes; D004365:Drugs, Chinese Herbal; D009466:Neuromuscular Blocking Agents; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; C051082:beta-eudesmol; D013390:Succinylcholine