EFFECT OF AN UPTAKE INHIBITOR ON SEROTONIN METABOLISM IN RAT-BRAIN - STUDIES WITH 3-PARA-TRIFLUOROMETHYLPHENOXY)-N-METHYL-3-PHENYLPROPYLAMINE (LILLY 110140)
EFFECT OF AN UPTAKE INHIBITOR ON SEROTONIN METABOLISM IN RAT-BRAIN - STUDIES WITH 3-PARA-TRIFLUOROMETHYLPHENOXY)-N-METHYL-3-PHENYLPROPYLAMINE (LILLY 110140)
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DOI：
10.1016/s0024-3205(74)80012-3
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发表时间：
1974-01-01
期刊：
影响因子：
6.1
通讯作者：
MOLLOY, BB
中科院分区：
文献类型：
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作者：
FULLER, RW;PERRY, KW;MOLLOY, BB
礼来公司110140是一种脑突触体摄取5-羟色胺的抑制剂。在大鼠中，它对大脑中色氨酸、5-羟色胺、多巴胺或去甲肾上腺素的水平没有影响，但它降低了5-羟基吲哚乙酸(5HIAA)的水平。5HIAA水平的降低与1-20 mg/kg的ip剂量有关。在剂量范围内，在10毫克/公斤剂量110140后持续至少24小时。5HIAA水平的下降主要发生在大脑半球和中脑，显然是由于5-羟色胺周转减少所致。在给予对氯苯丙胺抑制5-羟色胺合成后，脑内5-羟色胺水平下降的速度降低，表明周转减少。根据丙磺舒注射后5HIAA在脑内蓄积的速率计算，对照组大鼠的周转率为0.18μg/g/h，110140组为0.066μg/g/h。5-羟色胺转换率的下降可能是由于5-羟色胺在神经突触的再摄取(失活)被阻断而导致受体部位过度刺激时发生的一种代偿机制。
Lilly 110140 is an inhibitor of serotonin uptake by brain synaptosomes. In rats, it had no effect on brain levels of tryptophan, serotonin, dopamine, or norepinephrine, but it decreased 5-hydroxyindoleacetic acid (5HIAA) levels. The decrease in 5HIAA levels was dose-related over a 1–20 mg/kg i.p. dose range and persisted for at least 24 hrs after a 10 mg/kg dose of 110140. The decline in 5HIAA levels occurred mostly in the cerebral hemispheres and midbrain and apparently resulted from a reduced turnover of serotonin. Reduced turnover was indicated by a decreased rate of fall in brain serotonin levels after p-chlorophenylalamine was given to inhibit serotonin synthesis. Turnover rates calculated from the rate of 5HIAA accumulation in brain after probenecid injection were 0.18 μg/g/hr in control rats and 0.066 μg/g/hr in 110140-treated rats. The decline in serotonin turnover presumably is a compensatory mechanism occurring when receptor sites are overstimulated due to blockade of the reuptake (inactivation) of serotonin at the nerve synapse.