新抗肿瘤药氨三肼的药理研究

氨三肼(Nitrazine)灌胃及腹腔注射对大鼠W-256及小鼠L615白血病均有明显疗效,对腹水型W-256仅灌胃给药法有效;对小鼠ECS、HCS,脑瘤B22等亦有抗肿瘤作用,对S37及ARS则无疗效。维生素B6可取消氨三肼的抗W-256作用,维生素B6拮抗剂去氧吡哆醛(DOP)则可加强其作用。氨三肼对W-256的疗效与给药方案有关,一次给予维生素B6及去氧吡哆醛对氨三肼的LD_so没有明显影响。氨三肼的主要毒性反应表现在胃肠道,对体液免疫和细胞免疫无抑制作用。

Pharmacological Studies on Nitrazine,a Potential Antineoplastic Drug

Nitrazine (A1902),nitrolitriacetic hydrazide, exhibited good anti tumor activity against 1615 leukemia, ECS, HCS, brain tumor B22 in mice and W-256 carcinosarcoma in rats. It was ineffective against 837 and ARS in. mice. The antitumor effect of nitrazine on W-256 was schedule-dependent and could be antagonized by pyridoxine and potentiated by the deoxypyridoxine, a pyridoxine antagonist. With fixation. of the tetal dosage of 750 mg/kg ip, the tumor weight inhibition rate of nitrazine against W-256 was greater when it was administered every three days. The acute intraperitoneal LD50 for mice was 1736 mg/kg (1437-2035 mg/kg) and the oral LD50 in mice was 1343 mg/kg (1128-1559 mg/kg). A single dose of pyridoxine or deoxypyridoxine did not significantly affect the acute LD50 value of nitrazme. The subacute toxicity test of nitraxine in dogs showed that vomiting, bloody stool and cease of eating were the main toxic symptoms after intravenous or oral administration of nitrazine, but no toxic effect on bone marrow, liver and kidney function was noted. The hemolysin formation test, graft versus host reaction test and tumor concomitant immunity test were used to monitor the humoral- and cell-mediated immune function in mice. At the dosage of 250 mg/kg ip, no depressant effect oa both humoral and cell-mediated immunity was demonstrated.