美哌隆及其两种代谢产物与硫利达嗪对啮齿动物中枢单胺代谢及催乳素水平的影响。

Effect of melperone, two of its metabolites and thiothixene on central monoamine metabolism and prolactin levels in rodents.

作者信息

Wiesel F A, Bjerkenstedt L, Skett P

出版信息

Acta Pharmacol Toxicol (Copenh). 1978 Aug;43(2):129-36. doi: 10.1111/j.1600-0773.1978.tb02246.x.

DOI:10.1111/j.1600-0773.1978.tb02246.x

Abstract

The effects of melperone and thiothixene on the concentrations of monoamine metabolites in brain and prolactin in the serum of rats and mice were determined. Both drugs increased brain concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in a dose-dependent manner. 5-Hydroxyindoleacetic acid (5-HIAA) was unaffected. The effect of thiothixene was longer lasting and about 5 times greater than that of melperone. Melperone, but not thiothixene, increased levels of 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG). Several hours after administration of melperone, levels of HVA and MOPEG were diminished. Both drugs increased prolactin concentrations in rat serum. Thiothixene was about 10 times more potent than melperone. Of two urinary metabolites of melperone investigated, one caused the same qualitative effects on monoamine metabolism as melperone itself but with reduced potency. The other metabolite was ineffective.

摘要

测定了美哌隆和硫利达嗪对大鼠和小鼠脑内单胺代谢产物浓度及血清催乳素的影响。两种药物均以剂量依赖方式增加脑内二羟基苯乙酸（DOPAC）和高香草酸（HVA）的浓度。5-羟吲哚乙酸（5-HIAA）未受影响。硫利达嗪的作用持续时间更长，约为美哌隆的5倍。美哌隆可增加3-甲氧基-4-羟基苯乙二醇（MOPEG）水平，而硫利达嗪则无此作用。给予美哌隆数小时后，HVA和MOPEG水平降低。两种药物均增加大鼠血清催乳素浓度。硫利达嗪的效力约为美哌隆的10倍。在所研究的美哌隆的两种尿代谢产物中，一种对单胺代谢产生与美哌隆本身相同的定性作用，但效力降低。另一种代谢产物无效。