Datla K P, Curzon G
Department of Neurochemistry, Institute of Neurology, London, U.K.
Neuropharmacology. 1993 Sep;32(9):839-45. doi: 10.1016/0028-3908(93)90138-s.
The effects of the novel antidepressant tianeptine on behaviours induced by the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated. Tianeptine (10 mg/kg, i.p.) significantly attenuated wet dog shakes (WDS) induced by 5-HTP (75 mg/kg, i.p.; 30 min after carbidopa 25 mg/kg, i.p.). The effect was most marked when 5-HTP and tianeptine were given together. The main metabolite of tianeptine also attenuated WDS. Components of the 5-HT syndrome (i.e. reciprocal forepaw treading, hind limb abduction, flat body posture) induced by 8-OH-DPAT (0.5 mg/kg, s.c.) were unaffected by tianeptine and 5-HTP given both singly or together. However, tianeptine significantly reduced faecal pellet formation but not cage crossings resulting from 8-OH-DPAT administration. These cage crossings but not the associated faecal pellet formation were reduced by 5-HTP. This reduction was prevented by tianeptine. The increase of extracellular 5-HT in the frontal cortex following administration of 5-HTP was opposed and the concurrent increase of extracellular 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by tianeptine. The above behavioural and neurochemical findings indicate that tianeptine opposes the increase of 5-HT at receptor sites due to 5-HTP administration.
研究了新型抗抑郁药噻奈普汀对血清素（5-羟色胺，5-HT）前体5-羟色氨酸（5-HTP）及5-HT1A激动剂8-羟基-2-（二正丙基氨基）四氢化萘（8-OH-DPAT）诱导行为的影响。噻奈普汀（10毫克/千克，腹腔注射）显著减弱了由5-HTP（75毫克/千克，腹腔注射；在25毫克/千克卡比多巴腹腔注射30分钟后）诱导的湿狗颤抖（WDS）。当5-HTP和噻奈普汀同时给药时，这种作用最为明显。噻奈普汀的主要代谢产物也减弱了WDS。由8-OH-DPAT（0.5毫克/千克，皮下注射）诱导的5-HT综合征的组成部分（即前爪交替踏地、后肢外展、身体平躺姿势）不受噻奈普汀和5-HTP单独或联合给药的影响。然而，噻奈普汀显著减少了8-OH-DPAT给药导致的粪便颗粒形成，但不影响笼内穿行次数。5-HTP减少了这些笼内穿行次数，但不影响相关的粪便颗粒形成。噻奈普汀可防止这种减少。噻奈普汀对抗了5-HTP给药后额叶皮质细胞外5-HT的增加，并增强了细胞外5-羟吲哚乙酸（5-HIAA）的同时增加。上述行为和神经化学研究结果表明，噻奈普汀可对抗因5-HTP给药导致的受体部位5-HT增加。
