Watkins J B, Klaassen C D
Res Commun Chem Pathol Pharmacol. 1983 Mar;39(3):355-66.
A comparison of structure-choleretic activity relationship has been made for several branched- and straight-chain carboxylic acids including valproic acid. Cumulative bile flow was 13.8, 23.8, 29.4 and 14.9 ml/4hr/kg body weight for dimethyl-, diethyl-, dipropyl- (valproic acid), and dibutyl-acetic acid, respectively, after iv administration of approximately equimolar doses (1100 mumoles/kg). Except for dibutylacetic acid, maximal bile flow increased from control rates of 50-60 to 120-140 microliters/min/kg. Administration of higher doses of 2,2-dimethylbutanoic acid and 2-ethylbutanoic acid did not increase maximal bile flow above 125-140 microliters/min/kg but did prolong the duration of choleresis. Maximal and cumulative bile flows increased with length of carboxylic acid chain for 2,2-dimethyl substituted acids (2,2-dimethylacetic acid to 2,2-dimethylbutanoic acid). If the two methyl groups were on C-3 (3-methylbutanoic acid), no change in bile flow was observed. Straight-chain acids from C-5 to C-11 and pent-4-enoic acid did not alter bile flow. Thus, the effectiveness of several branched-chain carboxylic acids as choleretics parallel their ability as anticonvulsants. In contrast, the straight-chain acids which cause central nervous system depression have no choleretic activity.
已对包括丙戊酸在内的几种支链和直链羧酸的结构-利胆活性关系进行了比较。静脉注射大约等摩尔剂量（1100微摩尔/千克）后，二甲基、二乙基、二丙基（丙戊酸）和二丁基乙酸的累积胆汁流量分别为13.8、23.8、29.4和14.9毫升/4小时/千克体重。除二丁基乙酸外，最大胆汁流量从50 - 60微升/分钟/千克的对照速率增加到120 - 140微升/分钟/千克。给予更高剂量的2,2 - 二甲基丁酸和2 - 乙基丁酸并没有使最大胆汁流量增加到超过125 - 140微升/分钟/千克，但确实延长了利胆持续时间。对于2,2 - 二甲基取代的酸（2,2 - 二甲基乙酸到2,2 - 二甲基丁酸），最大和累积胆汁流量随羧酸链长度增加。如果两个甲基在C - 3位（3 - 甲基丁酸），则未观察到胆汁流量变化。从C - 5到C - 11的直链酸和戊 - 4 - 烯酸不会改变胆汁流量。因此，几种支链羧酸作为利胆剂的有效性与其作为抗惊厥剂的能力相当。相比之下，引起中枢神经系统抑制的直链酸没有利胆活性。
