Matera G, Chisari M, Altavilla D, Foca A, Cook J A
Istituto di Microbiologia Medica, Università di Messina, Italy.
Proc Soc Exp Biol Med. 1988 Jan;187(1):58-61. doi: 10.3181/00379727-187-42637.
The efficacy of N,N'-bis-(3-picolyl)-methoxyisophthalamide (picotamide) as an in vitro thromboxane synthetase inhibitor and its effect on endotoxin (LPS)-induced lethality in rats were assessed. Picotamide at 0.5 and 1.0 mM concentrations significantly (P less than 0.05) inhibited basal and LPS-stimulated synthesis of TxA2 measured by its stable immunoreactive (i) metabolite TxB2 in rat peritoneal macrophages. This compound did not inhibit synthesis of i6-keto-PGF1 alpha, the stable metabolite of PGI2, and produced significant shunting to i6-keto-PGF1 alpha. For lethality studies rats were pretreated, by gavage with picotamide, at either 75, 150, 300, or 600 mg/kg 2 hr prior to iv S. enteritidis (LPS, 20 mg/kg). Both 150 and 300 mg/kg doses of picotamide significantly (P less than 0.05) improved survival in endotoxin shock at 48 hr. These studies demonstrate that picotamide is a selective thromboxane synthetase inhibitor, and that it may be useful during disease states characterized by increased TxA2 synthesis.
评估了N，N'-双（3-吡啶甲基）-间苯二甲酰胺（匹可托胺）作为体外血栓素合成酶抑制剂的功效及其对大鼠内毒素（LPS）诱导的致死率的影响。浓度为0.5和1.0 mM的匹可托胺能显著（P<0.05）抑制大鼠腹腔巨噬细胞中通过其稳定的免疫反应性（i）代谢物TXB2测量的基础和LPS刺激的TX A2合成。该化合物不抑制PGI2的稳定代谢物i6-酮-PGF1α的合成，并导致明显转向i6-酮-PGF1α。在致死率研究中，大鼠在静脉注射肠炎沙门氏菌（LPS，20 mg/kg）前2小时，通过灌胃给予75、150、300或600 mg/kg的匹可托胺进行预处理。150和300 mg/kg剂量的匹可托胺均能显著（P<0.05）提高48小时内毒素休克的存活率。这些研究表明，匹可托胺是一种选择性血栓素合成酶抑制剂，并且在以TX A2合成增加为特征的疾病状态下可能有用。
