Imanishi N, Murakami-Uchida M, Koike H, Natsume Y, Morooka S
Research Laboratories, Sumitomto Pharmaceuticals Co., Ltd., Osaka, Japan.
Arzneimittelforschung. 1994 Mar;44(3):317-22.
SM-12502 ((+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl, CAS 119383-00-5) inhibited platelet-activating factor (PAF)-induced aggregation of rabbit and human platelets with IC50 values of 2.3 mumol/l and 4.7 mumol/l, respectively, but did not inhibit platelet aggregation induced by adenosine diphosphate, collagen, thrombin, arachidonic acid, U46619 (a thromboxane A2 agonist) or Ca2+ ionophore A23187 at concentrations up to 400 mumol/l. SM-12502 competitively antagonized 3H-PAF binding to rabbit platelets with an IC50 of 1.0 mumol/l. In contrast, the anti-PAF activity of the optical isomer SM-12501 ((-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl) was much weaker and its IC50 was more than 100 mumol/l. SM-12502 prevented PAF-induced death in mice with ID50 values of 4.8 mg/kg (i.v.) or 68.6 mg/kg (p.o.). In guinea pigs, SM-12502 inhibited PAF (0.1 micrograms/kg)-induced hemoconcentration with ID50 values of 1.9 mg/kg (i.v.) or 40.2 mg/kg (p.o.). In addition, SM-12502 inhibited PAF (10 ng/kg)-induced hypotension in rats with ID50 values of 2.0 mg/kg (i.v.) or 6.5 mg/kg (p.o.). The in vivo effects of SM-12501 were much weaker. Orally administered SM-12502 showed rapid absorption and a long duration of pharmacological activity in rats. SM-12502 afforded dose-dependent protection against anaphylactic death in mice with ID50 values of 18.4 mg/kg (i.v.) and 136 mg/kg (p.o.). It also inhibited endotoxin (E. coli 0.55:B5, 60 mg/kg)-induced death in mice, with ID50 values of 119 mg/kg (i.v.) and 182 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)
SM - 12502（（+）-顺式-3,5-二甲基-2-（3-吡啶基）噻唑烷-4-酮盐酸盐，CAS 119383 - 00 - 5）抑制血小板活化因子（PAF）诱导的兔和人血小板聚集，IC50值分别为2.3 μmol/L和4.7 μmol/L，但在浓度高达400 μmol/L时，不抑制二磷酸腺苷、胶原、凝血酶、花生四烯酸、U46619（一种血栓素A2激动剂）或Ca2 +离子载体A23187诱导的血小板聚集。SM - 12502以1.0 μmol/L的IC50竞争性拮抗3H - PAF与兔血小板的结合。相比之下，光学异构体SM - 12501（（-）-顺式-3,5-二甲基-2-（3-吡啶基）噻唑烷-4-酮盐酸盐）的抗PAF活性弱得多，其IC50超过100 μmol/L。SM - 12502预防PAF诱导的小鼠死亡，静脉注射ID50值为4.8 mg/kg，口服为68.6 mg/kg。在豚鼠中，SM - 12502抑制PAF（0.1微克/千克）诱导的血液浓缩，静脉注射ID50值为1.9 mg/kg，口服为40.2 mg/kg。此外，SM - 12502抑制PAF（10纳克/千克）诱导的大鼠低血压，静脉注射ID50值为2.0 mg/kg，口服为6.5 mg/kg。SM - 12501的体内作用弱得多。口服给药的SM - 12502在大鼠中显示出快速吸收和长时间的药理活性。SM - 12502对小鼠过敏性死亡提供剂量依赖性保护，静脉注射ID50值为18.4 mg/kg，口服为136 mg/kg。它还抑制内毒素（大肠杆菌0.55:B5，60 mg/kg）诱导的小鼠死亡，静脉注射ID50值为119 mg/kg，口服为182 mg/kg。（摘要截断于250字）
