Different modes of potentiation by beta-eudesmol, a main compound from Atractylodes lancea, depending on neuromuscular blocking actions of p-phenylene-polymethylene bis-ammonium derivatives in isolated phrenic nerve-diaphragm muscles of normal and alloxan-diabetic mice.
The essential moieties in p-phenylene-polymethylene bis-ammonium (PMBA) derivatives, C6H4[X(CH2)nN+R3]2, on the potentiating effects by beta-eudesmol, a main component of Atractylodes lancea, of their neuromuscular blockades were investigated in isolated phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. PMBA derivatives were separated into the following three groups based on the patterns of the potentiating effects: group I: PMBA-23 (n = 6, R = Me) and PMBA-24 (n = 6, R = Et); group II: PMBA-1 (n = 4, R = Me), PMBA-21 (n = 4, R = Et) and PMBA-2 (X = O, n = 3, R = Me); and group III: PMBA-31 (X = S, n = 3, R = Me), PMBA-3 (X = CO, n = 3, R = Me) and PMBA-4 (X = CHOH, n = 3, R = Me). The pretreatment with 80 microM beta-eudesmol for 60 min did not affect group I-induced neuromuscular blocking action, and it potentiated group II- and group III-induced ones. The potentiating effect of beta-eudesmol on group III was greater in diabetic muscles than in normal one and that on group II was to the same extent in both muscles. These results suggest that the four-methylene length of the side chains in normal muscles and the hydrophilic moieties adjacent to a phenylene ring in diabetic muscles are related to the potentiating effect by beta-eudesmol on PMBA derivatives.
Kimura
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Kimura
I
I
Muroi
M
M
Tanaka
K
K
Nojima
H
H
Uwano
T
T
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003964:Diaphragm / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D010791:Phrenic Nerve / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D045787:Sesquiterpenes, Eudesmane; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000494:pharmacology*
D009466:Neuromuscular Blocking Agents; D000644:Quaternary Ammonium Compounds; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; C051082:beta-eudesmol