Potentiating effects of β-eudesmol-related cyclohexylidene derivatives on succinylcholine-induced neuromuscular block in isolated phrenic nerve-diaphragm muscles of normal and alloxan-diabetic mice

Article abstract of DOI:10.1248/bpb.18.407

β-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 β-eudesmol-related cyclohexylidene derivatives (2-(3-hydroxy-3-methylbutyl)cyclohexylidene KTE-13, 2-(3-hydroxy-3-methylbutyl)-4-cyclohexyl 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 μM) 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 μM) and -32 (200 μM) 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.

Full text of DOI:10.1248/bpb.18.407

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service