Björk L, Mellin C, Hacksell U, Andén N E
Department of Medical Pharmacology, Biomedical Center, Uppsala, Sweden.
Eur J Pharmacol. 1987 Nov 3;143(1):55-63. doi: 10.1016/0014-2999(87)90734-5.
The effects of the four possible C3-methylated stereoisomers of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) ((-)-CM-11, (+)-CM-11, (-)-CM-12, (+)-CM-12) on brain 5-hydroxytryptamine (5-HT) receptor functions were studied in rats. (-)-CM-11 and (+)-CM-12 inhibited dose dependently in all brain parts the accumulation of 5-hydroxytryptophan following decarboxylase inhibition. Their antipodes were inactive. The disappearance of 5-HT induced by alpha-propyldopacetamide was retarded by (-)-CM-11 and (+)-CM-12. The biochemically active isomers produced a flat body posture and forepaw treading. The results indicate that (-)-CM-11 and (+)-CM-12 stimulate 5-HT receptors directly although not as potently as 8-OH-DPAT. The concentration of dopamine was lowered and that of homovanillic acid was elevated by (+)-CM-11 and by both enantiomers of CM-12 in the corpus striatum and in the limbic system of rats. The accumulation of DOPA following decarboxylase inhibition was not markedly changed by any of the compounds. Locomotor activity was enhanced by (+)-CM-11 but not by any of the other compounds, and the effect was haloperidol-resistant. (+)-CM-11 induced no asymmetry in rats in which the corpus striatum was inactivated on one side. Thus, none of the isomers of CM-11 or CM-12 appears to have any effect on the dopamine receptors.
研究了8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）的四种可能的C3-甲基化立体异构体（（-）-CM-11、（+）-CM-11、（-）-CM-12、（+）-CM-12）对大鼠脑5-羟色胺（5-HT）受体功能的影响。（-）-CM-11和（+）-CM-12在所有脑区均剂量依赖性地抑制脱羧酶抑制后5-羟色氨酸的蓄积。它们的对映体无活性。（-）-CM-11和（+）-CM-12可延缓α-丙基多巴胺酰胺诱导的5-HT消失。具有生化活性的异构体可产生平卧式体位和前爪踏地动作。结果表明，（-）-CM-11和（+）-CM-12直接刺激5-HT受体，尽管其效力不如8-OH-DPAT。在大鼠纹状体和边缘系统中，（+）-CM-11以及CM-12的两种对映体均可降低多巴胺浓度并升高高香草酸浓度。脱羧酶抑制后多巴的蓄积未被任何一种化合物显著改变。（+）-CM-11可增强运动活性，但其他化合物均无此作用，且该作用对氟哌啶醇耐药。（+）-CM-11在一侧纹状体失活的大鼠中未诱导不对称性。因此，CM-11或CM-12的任何异构体似乎对多巴胺受体均无影响。
