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31.
Hassib A. Sahyoun Brenda Costall Robert J. Naylor 《Naunyn-Schmiedeberg's archives of pharmacology》1982,319(1):8-11
Summary Dopamine was shown to act on the circular smooth muscle of the stomach body to cause contraction at a yohimbine-sensitive site (2) and a relaxation at a prazosin-sensitive site (1). Metoclopramide and tiapride failed to modify either response, failed to antagonise a relaxation to phenylephrine at 1(1 sites in the same tissue, and failed to modify the contractions caused by dopamine and phenylephrine at an 2-adrenoceptor site in the pyloric sphincter. However, (+)- and (–)-sultopride and (+)-sulpiride antagonised the dopamine-induced contractions of the stomach body indicating an 2-antagonist action. An ability to attenuate the relaxation of this tissue may reflect a displacement of the contraction curve to the right rather than an 2-antagonist action since the response to phenylephrine was not antagonised either in this tissue or in the pyloric sphincter. Within the central nervous system the (–)-enantiomers of sultopride and sulpiride have a highly selective dopamine receptor blocking action. This cotrasts with the present findings in the stomach musculature of a non-stereospecific antagonism at 2-type adrenoceptors. 相似文献
32.
Summary The lipolytic and hyperglycaemic actions of three xanthine derivatives of dopamine were studied in fed rats by determining the plasma levels of glycerol, free fatty acids and glucose. All three derivatives, 7-propyl-theophylline-dopamine, 7-(3-methyl)-propyl-theophylline-dopamine and 7-(2-methyl)-propyl-theophilline-dopamine, had a longer duration of action on lipolysis than had dopamine. These xanthine derivatives stimulated lipolysis at 10-to 100-times lower doses than dopamine and also had a greater maximal effect. Glycogenolysis was stimulated by 7-(3-methyl)- and 7-(2-methyl)-propyl-theophyllinedopamine at lower doses than by dopamine, the maximal effect, however, being smaller than that of dopamine. 7-propyl-theophylline-dopamine had practically no hyperglycaemic effect. Pretreatment with the -adrenoceptor blocking agents, phentolamine and dihydroergotamine, blocked the increase of the plasma level of glucose induced by dopamine, whereas the hyperglycaemic effect of 7-(3-methyl)-propyl-theophylline-dopamine was better antagonized by the -adrenoceptor blocking agent, propranolol. The -adrenoceptor antagonists had no clearcut effects on the lipolytic action of dopamine or its xanthine derivatives, which was, however, clearly antagonized by pretreatment with propranolol. Desipramine and reserpine, at doses which prevented the metabolic actions of tyramine, partially blocked the lipolytic and hyperglycaemic effect of dopamine, but not those of the xanthine derivatives. This suggests that the xanthine derivatives- in contrast to dopamine- do not have an indirect, tyramine-like component in their metabolic actions. Pretreatment with pargyline, an inhibitor of monoamine oxidase, strongly enhanced the metabolic effects of dopamine, but to a lesser extent the actions of its xanthine derivatives, indicating that these derivatives are more resistant to monoamine oxidase than is dopamine. The results indicate that the xanthine derivatives have metabolic effects similar to those of dopamine, but differ from dopamine in their activity and relative affinity with respect to metabolic - and -adrenoceptors and in their mechanism of action as well as in their metabolism.Deceased August 6, 1978 相似文献
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目的 设计合成具有抗菌活性的诺氟沙星衍生物。方法 采用2-甲基-5-硝基咪唑、诺氟沙星等为原料,通过亲核取代反应合成目的物;测定目的物的体内抗菌活性。结果 合成的9个化合物的结构经MS、^1H-NMR和元素分析所确证。结论 合成了9个未见报道的新化合物,体内活性测试结果表明:其中的3个化合物具有较高的抗菌活性。 相似文献
37.
四氢异喹啉衍生物的合成及抗真菌活性 总被引:2,自引:0,他引:2
目的 寻找新的抗真菌活性化合物。方法 采用Pictet-Spengler法合成四氢异喹啉,再通过氮直接烃化法合成目标化合物,并对目标化合物进行初步的体外抗真菌活性实验。结果 合成了18个新的四氢异喹啉衍生物,利用红外光谱、核磁共振谱进行了结构确认。结论 所合成的18个四氢异喹啉衍生物具有不同程度的抗真菌活性。 相似文献
38.
目的 设计合成3-溴-4-硫色(满)酮类化合物,并对其抗真菌活性进行初步评价。方法 以取代硫色(满)酮为原料,经溴化、氧化等反应制得目标化合物,化合物的体外抗真菌活性测定采用二倍浓度稀释法。结果 共合成了9个未见文献报道的新化合物,经红外光谱、核磁共振氢谱及元素分析确证其结构。其中化合物Vb的活性好于或相当于对照药。结论 硫色(满)酮3-位溴取代后具有较强的抗真菌活性。 相似文献
39.
白花前胡丙素C-3′和C-4′反式结构类似物的半合成白花前胡丙素C-3′和C-4′反式结构类似物的半合成 总被引:3,自引:0,他引:3
目的对白花前胡丙素[(+)-praeruptorin A]进行结构修饰,半合成C-3′和C-4′反式结构类似物,寻找活性化合物。方法首先从白花前胡(Peucedanum praeruptorum)根中分离得到白花前胡丙素,从白花前胡丙素出发,运用碱水解及各种酰化反应,半合成各种结构修饰产物。结果首次合成了17个白花前胡丙素C-3′和C-4′反式结构类似物,通过IR,1HNMR,MS等方法确定它们的结构。结论17个化合物均为新化合物,其中一些新化合物有显著的钙离子拮抗活性,首次证明C-3′和C-4′反式结构的这类化合物同样具有活性。 相似文献
40.
A toxicokinetic model of malathion and its metabolites as a tool to assess human exposure and risk through measurements of urinary biomarkers. 总被引:2,自引:0,他引:2
Michèle Bouchard Nathalie H Gosselin Robert C Brunet Onil Samuel Marie-Josée Dumoulin Gaétan Carrier 《Toxicological sciences》2003,73(1):182-194
A toxicokinetic model is proposed to predict the time evolution of malathion and its metabolites, mono- and dicarboxylic acids (MCA, DCA) and phosphoric derivatives (dimethyl dithiophosphate [DMDTP], dimethyl thiophosphate [DMTP], and dimethyl phosphate [DMP]) in the human body and excreta, under a variety of exposure routes and scenarios. The biological determinants of the kinetics were established from published data on the in vivo time profiles of malathion and its metabolites in the blood and urine of human volunteers exposed by intravenous, oral, or dermal routes. In the model, body and excreta compartments were used to represent the time varying amounts of each of the following: malathion, MCA, DCA, DMDTP, DMTP, and DMP. The dynamic of intercompartment exchanges was described mathematically by a differential equation system that ensured conservation of mass at all times. The model parameters were determined by statistically adjusting the explicit solution of the differential equations to the experimental human data. Simulations provide a close approximation to kinetic data available in the published literature. When simulating a dermal exposure to malathion, the main route of entry for workers, the model predicts that it takes an average of 11.8 h to recover half of the absorbed dose of malathion eventually excreted in urine as metabolites, compared to 3.2 h following an intravenous injection and 4.0 h after oral administration. This shows that following a dermal exposure, the absorption rate governs the urinary excretion rate of malathion metabolites because the dermal absorption rate is much slower than biotransformation and renal clearance processes. The model served to establish biological reference values for malathion metabolites in urine since it allows links to be made between the absorbed dose of malathion and the time course of cumulative amounts of metabolites excreted in urine. From the no-observed-effect level (NOEL) of 0.61 micromol/kg/day derived from the data of Moeller and Rider (1962), the model predicts corresponding biological reference values for MCA, DCA, and phosphoric derivatives of 44, 13, and 62 nmol/kg, respectively, in 24-h urine samples. The latter were used to assess the health risk of workers exposed to malathion in botanical greenhouses, starting from urinary measurements of MCA and DCA metabolites. 相似文献