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用伯氏鼠疟模型筛选了17个2,4-二氨基-6-取代氨基磺酰喹唑啉类化合物。初步结果显示,化合物Ⅰ4,Ⅰ5,Ⅰ10,Ⅰ11和Ⅰ12口服有较好抗疟作用,对正常敏感株(N)的SD50为0.43~2.4mg/kg×4d,高度抗氯喹株(RC)为0.19~0.42mg/kg×4d,(NK65)株为7.2~100mg/kg×4d,抗磺胺株(ORA)为11~76 mg/kg×4d。上述结果表明,该类化合物对(RC)株的疗效显著优于(N)株,但对(NK65)株的疗效较差,与磺胺类药物有轻度交叉抗性。 相似文献
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本文建立了血浆中硝硫苯酯TLC扫描定量法,并可同时测定血浆中代谢物硝硫氰胺浓度。该法专一、灵敏。大鼠单剂ig硝硫苯酯200mg/kg后,血浆硝硫苯酯Cmax为0.510μg.ml-1,tmax为6 h,药—时曲线符合二室模型。t1/2ka,t1/2a、t1/2β分别为1.503,2.829和17.769 h;k10,k21和k12分别为0.068,0.141和0.075h-1,∫0∞cdt为12.367μg·h·ml-1。本文还证明硝硫苯酯在吸收后,有部分转变为硝硫氰胺,其Cmax为0.283μg·ml-1,tmax为6 h。硝硫苯酯和硝硫氰胺曲线下∫036cdt分别为9.211和4.644μg·h·ml-1,后者约为前者的50%。 相似文献
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目的 研究哌嗪类新化合物1,6-二( 4-苯乙基1-甲基-1-哌嗪基)己烷二溴化物(97-9-G4)的镇痛作用及机制。方法 扭体法、热板法研究镇痛活性;联合给药观察纳洛酮、利血平、阿托品、CaCl2和EDTA等对97-9G4镇痛作用的影响;并测定97-9-G4对小鼠体内PGE2的影响。结果 sc 97-9-G4 5mg/kg即可有效抑制小鼠扭体反应(P<0.05) ;sc 40mg/kg和icv 2.5μg/kg均可明显延长热板实验的舔足阈(P<0.05) ;纳洛酮、CaCl2和EDTA均可拮抗、减弱或加强其镇痛作用;利血平、阿托品对97-9-G4的镇痛作用影响不明显。结论 97-9-G4具有明显的镇痛活性,其镇痛作用与阿片受体及体内Ca2+等因素有一定关系。 相似文献
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本文报道了6个4-甲基-5取代苯氧基-6-甲氧基-8-(1-甲基-4-氨基丁氨基)喹啉(Ⅲ)的合成。除Ⅲ3外,所有化合物对鼠疟P.berghei的抑制性治疗作用和对鼠疟P.yoelii的病因性预防作用均优干伯喹,其中以Ⅲ1最强。Ⅲ1口服治疗作用的SD50和SD90分别为0.65 mg/kg和1.60 mg/kg,口服预防作用的最小有效剂量(MED)和最小完全有效剂量(MFAD)分别为2.5mg/kg和5.0 mg/kg。对这类化合物的根治作用和毒性试验正在进行中。 相似文献
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硝硫苯酯及其有关硫代氨基甲酸衍生物的合成和抗日本血吸虫作用 总被引:1,自引:0,他引:1
本文报道22个4-硝基二苯胺-4′-硫代氨基甲酸衍生物和其二苯醚二苯硫醚类似物的合成,大多数化合物为氨基甲(?)酸芳酯。筛选结果表明4-硝基二苯胺-4′-氨基甲(?)酸芳酯和二苯醚类似物有较强的抗日本血吸虫作用而二苯硫醚类似物则无明显的抗虫作用。4-硝基二苯胺-4′-氨基甲(?)酸苯酯——硝硫苯酯(代号7720)已作为抗日本血吸虫病药物在临床试用,证明其疗效较高,毒性较低。本文还简要讨论了结构和抗日本血吸虫作用的关系。 相似文献
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本文报道标题化合物的合成及其抗疟、抗肿瘤和抗菌活性,该类化合物是以5-氯-2,4, 6-三氨基喹唑啉与各种取代苯甲醛缩合成相应的Schiff碱,然后经NaBH4还原,再甲酰化或亚硝化制得.经对感染伯氏疟原虫(P.berghei)的鼠抑制性治疗筛选,有八个化合物剂量20mg/kg×4d时抑制率100%,Ⅰ3,Ⅰ4,Ⅲ4三个化合物剂量5mg/kg×4d时抑制率在90%以上;体外抗肿瘤试验有4个化合物的活性优于MTX和SIPl759,以Ⅰ4最佳。对L1210白血病细胞株的IC50为2.20×10-9 m mol/L;经对18种常用菌株进行体外筛选,发现对肺炎双球菌(D.pneumoniae)有较好的活性。 相似文献
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吡喹酮对感染日本血吸虫小鼠与家兔的疗效和血药浓度的关系 总被引:1,自引:0,他引:1
本文报道小鼠与家兔感染日本血吸虫后不同时间用吡喹酮ig或im治疗,其疗效与周用血药浓度无密切的平行关系。在疗效相仿的剂量下,感染4wk鼠给药后的最高血药浓度达20.2μg/ml,而感染 4wk兔的血药浓度仅为0.05μg/ml。从感染兔的十二指肠注人吡喹酮时,则门静脉的血药浓度最高可达15~25μg/ml。结果显示感染宿主ig吡喹酮治疗时,门静脉的血药浓度可能在吡喹酮杀虫过程中具有重要意义。 相似文献
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M. Chvdoff J. M. Faccini M. H. Gregory R. M. Hull A. M. Monro J. Perraud R. M. Quinton H. H. Reinert 《Drug development research》1984,4(2):229-235
Oxamniquine displayed low acute toxicity in mice, hamsters, and rabbits. In rats, however, oxamniquine was much more toxic, the female being 8–10 times more sensitive than the male; single doses elicited an idiosyncratic sex-linked hepatic necrosis and bile duct proliferation. Dogs given repeated oral doses of 20 or 30 mg/kg/day for 5 successive days every 4 weeks for 11 months showed neurological disturbances of short duration, which tended gradually to increase in severity from one dosage period to the next; no histopathological correlate could be found. In chronic studies in mice (18 months) and hamsters (19 months) with intermittent dosage regimens relevant to likely usage in man, no evidence of carcinogenicity potential was observed at dose levels up to 150 mg/kg. Oxamniquine displayed no maternal toxicity or teratogenicity in mice and rabbits, and only slight embryotoxicity after high oral doses. 相似文献
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口服硝唑咪衍生物S 72014对小鼠血吸虫病的化疗指数为21.2,较硝唑咪的5.8为大。病兔用S 72014 50~200mg/kg/天的2~14天疗法治疗时,减虫率均在90%以上。感染犬与猴每天用S 72014,125~210 mg/kg治疗,3次分服,疗程为7~14天时,均获得治愈。S 72014对小鼠的毒性较硝唑咪的低9倍以上。S 72014对小鼠和犬的中枢神经系统的作用较硝唑咪的为轻。在所用的剂量下,S 72014对犬与猴的肝、肾功能无明显影响,对心电图则引起暂时性的S-T段压低和T波平坦。较大剂量的S 72014对犬与猴的中枢神经系统、肝及肾有暂时性的病理损害,且明显抑制雄性动物的生精过程。S 72014与硝唑咪对犬可引起严重的再生障碍性贫血,但对猴的造血功能则无影响。 相似文献
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SCHOENIG GERALD P.; NEEPER-BRADLEY TERESA L.; FISHER LOUAN C.; HARTNAGEL RALPH E. JR. 《Toxicological sciences》1994,23(1):63-69
The potential for DEET to produce developmental toxicity wasevaluated in Charles River CD rats and New Zealand White rabbits.Rats were administered undiluted DEET by gavage on GestationalDays (gd) 615 at dosage levels of 0, 125, 250, and 750mg/kg/day. Rabbits were administered undiluted DEET by gavageon gd 618 at dosage levels of 0, 30, 100, and 325 mg/kg/day.Group sizes were 25 females per group for rats and 16 femalesper group for rabbits. Control rats and rabbits were ad ministeredcorn oil at the same dosage volumes administered in the high-doseDEET groups. In rats, maternal toxicity in the form of clinicalsigns including two deaths and depressed body weight and foodconsumption was observed at the high-dose level of 750 mg/kg/day.Rat fetal body weights per litter also were reduced at 750 mg/kg/day.In rabbits, maternal toxicity in the form of depressed bodyweight and food consumption was observed at the high-dose levelof 325 mg/kg/day. No maternal toxicity was observed at the low-or mid-dose groups for rats or rabbits. With the exception ofthe reduced fetal weights in rats at 750 mg/kg, there was noevidence of fetal toxicity, no effects on any of the gestationalparameters, nor were there any treat ment-related increasesin external, visceral, or skeletal variations or malformationsin the offspring from the rats and rabbits from these studies.1994 Society of Toxicology. 相似文献
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吡喹酮衍生物′S77078、S78015、S79046和21542对小鼠血吸虫均有明显的杀死作用。S78015、S79046和21542的剂量为200~400mg/kg/d,疗程2天,对病鼠的减虫率分别为22.5~53.9%、27.6%和32.8~66.9%;S77078 200~600mg/kg/d,疗程1~2天的减虫率为60.1~97.3%,与吡喹酮的83.6~95.6%的相近似。当S77078每天总剂量为30~60mg/Kg、疗程1~2天,对病兔和病犬的减虫率分别为18.3~40.8%和53.7~80.4%,均较吡喹酮的30~60mg/kg×1天的97.1~97.3%和89.7~98.5%的为低。 相似文献
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人参对接种锥虫的小鼠,能延缓锥虫在小鼠血中出现的时间,且能使小鼠耐受更多的锥虫,显著地延长其生存时间。此种作用随着感染前给药的时间延长而增强。人参对健康家兔体温没有影响,但长期喂药,却能防止靜脉注射菌苗引起的发热反应。在麻醉犬的实验中,人参能对抗磷酸组织胺引起的血压降低及肠管兴奋作用。 相似文献
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《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(11):1461-1471
1. Hexobarbital (100?mg/kg i.p.) sleeping times in male CD-1 mice pretreated (-1?h) with a single i.p. injection of 150 μmol/kg of psoralen or coumarin analogues were increased, most markedly (6-fold) by linear, methoxy-substituted psoralens.2. Hexobarbital sleeping times of mice which received three daily injections (231 μmol/kg; 50?mg/kg) of 8-methoxypsoralen (8-MOP) were 44% of controls (corn oil).3. The whole-body half-life of caffeine (1?mg) in mice was 10˙2, 1˙2, and 0˙37?h following 8-MOP (50?mg/kg per day) × 1, vehicle, and 8-MOP × 3 respectively.4. The whole-body concentrations of hexobarbital (100?mg/kg dose) in mice 30?min after dosing were 14˙3±0˙9, 8˙4±0˙3, and 5˙2±0˙5 μg/ml (1 mcuse = 150 ml) following 8-MOP (50?mg/kg per day) × 1, vehicle, and 8-MOP × 3 respectively.5. It is concluded that, administered acutely, psoralen analogues inhibit hexobarbital metabolism in mice; and 8-MOP administered acutely inhibits the metabolism of caffeine and hexobarbital, but administered repeatedly increases their metabolism. 相似文献