STUDIES ON INHIBITION OF HISTIDINE DECARBOXYLASE, AROMATIC-L-AMINO ACID DECARBOXYLASE AND ACID SECRETION BY BROCRESINE AND ITS METABOLITES
STUDIES ON INHIBITION OF HISTIDINE DECARBOXYLASE, AROMATIC-L-AMINO ACID DECARBOXYLASE AND ACID SECRETION BY BROCRESINE AND ITS METABOLITES
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DOI：
10.1016/0006-2952(73)90218-9
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发表时间：
1973-01-01
影响因子：
5.8
通讯作者：
STUBBS, CS
中科院分区：
文献类型：
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作者：
ELLENBOGEN, L;KELLY, RG;STUBBS, CS
Brocresine (NSD 1055) 在体内快速代谢。可能的代谢物是4-溴-3-羟基-苯甲醇、4-溴-3-羟基-苯甲酸和4-溴-3-羟基-马尿酸。溴甲辛和这些代谢物在体外抑制大鼠胎儿和大鼠胃组氨酸脱羧酶（l-组氨酸羧化酶，EC 4.1.1.22），两种酶的摩尔 I 50 分别约为 10-8、10-4、10-3 和 10-5。 Brocresine 及其代谢物还在体外抑制来自猪肾和大鼠胃粘膜的芳香族-L-氨基酸脱羧酶（3, 4-二羟基-L-苯丙氨酸羧化酶 EC 4.1. 1.26），两种酶的摩尔 I 50 分别约为 10− 7、10− 4、10− 3 和 10− 3。西兰花碱、乙醇代谢物和酸性代谢物腹腔注射200 mg·kg后对大鼠胃组氨酸脱羧酶有抑制作用，而马尿酸盐仅具有弱抑制作用。所有四种化合物均抑制幽门结扎大鼠的胃酸分泌，但胃酸和马尿酸盐仅具有中等抑制作用。血红蛋白与溴己新反应形成高铁血红蛋白，很容易解释药物抑制活性的快速消失。
Brocresine (NSD 1055) is rapidly metabolized in vivo. The probable metabolites are 4-bromo-3-hydroxy-benzyl alcohol, 4-bromo-3-hydroxy-benzoic acid and 4-bromo-3-hydroxy-hippuric acid. Brocresine and these metabolites inhibit both rat fetal and rat gastric histidine decarboxylase (l-histidine carboxylase, EC 4.1. 1.22) in vitro with a molar I 50 of about 10− 8, 10− 4, lO− 3 and 10− 5, respectively, for both enzymes. Brocresine and the metabolites also inhibit aromatic-l-amino acid decarboxylase (3, 4-dihydroxy-l-phenylalanine carboxylase EC 4.1. 1.26) from hog kidney and rat gastric mucosa in vitro with a molar I 50 of about 10− 7, 10− 4, 10− 3 and 10− 3, respectively, for both enzymes. Brocresine, the alcohol metabolite and the acid metabolite inhibited rat gastric histidine decarboxylase after intraperitoneal administration of 200 mg kg, whereas the hippurate was only weakly inhibitory. All four compounds inhibited gastric acid secretion in the pylorus-ligated rat, but the acid and hippurate were only moderately inhibitory. The reaction of hemoglobin with brocresine to form methemoglobin readily explains the rapid disappearance of the inhibitory activity of the drug.