Hong M, Roots E J, Jenner P, Marsden C D
MRC Movement Disorders Research Group, University Department of Neurology, London, U.K.
Neuropharmacology. 1988 May;27(5):519-27. doi: 10.1016/0028-3908(88)90135-9.
The effect of chlorpromazine, oxypertine, tetrabenazine or reserpine on alpha-adrenoreceptors and 5-HT2 receptors in the brain of the rat was studied both in vitro and after the administration to animals for up to 12 months. In vitro, chlorpromazine and oxypertine potently displaced the specific binding of [3H]WB 4101 to alpha 1 adrenoreceptors in the cortex and of [3H]ketanserin to 5-HT2 receptors in the frontal cortex. Both drugs were moderately effective in displacing the specific binding of [3H]clonidine from cortical alpha 2-adrenoreceptors. Tetrabenazine only weakly displaced the specific binding of [3H]WB 4101, [3H] clonidine and [3H]ketanserin. The incorporation of reserpine into tissue incubates had little effect on the binding of any of these ligands. Administration of chlorpromazine (33-36 mg/kg/day) to rats for up to 12 months reduced the number of specific binding sites (Bmax) for [3H]ketanserin in the frontal cortex, but did not alter the specific binding of [3H]WB 4101 or specific [3H]clonidine to cortical membranes. In contrast, treatment with oxypertine (6.3-7.3 mg/kg/day), tetrabenazine (6.0-6.7 mg/kg/day) or reserpine (0.28-0.30 mg/kg/day) increased the Bmax for the specific binding of [3H]WB 4101, but did not alter the specific binding of [3H]clonidine or [3H]ketanserin. Oxypertine resembles chlorpromazine in its ability to interact with alpha-adrenoreceptors and 5-HT2 receptors in brain. Tetrabenazine and reserpine have few direct actions on post-synaptic monoamine receptors. However, on long-term administration, oxypertine, like tetrabenazine and reserpine, predominantly altered alpha 1-adrenoreceptors, whereas chlorpromazine influenced the population of 5-HT2 receptors.
研究了氯丙嗪、奥昔哌汀、丁苯那嗪或利血平对大鼠脑内α-肾上腺素能受体和5-HT2受体的影响，包括体外实验以及对动物给药长达12个月后的实验。在体外，氯丙嗪和奥昔哌汀能有效取代[3H]WB 4101与皮质α1肾上腺素能受体的特异性结合，以及[3H]酮色林与额叶皮质5-HT2受体的特异性结合。两种药物在取代[3H]可乐定与皮质α2肾上腺素能受体的特异性结合方面效果中等。丁苯那嗪仅能微弱地取代[3H]WB 4101、[3H]可乐定和[3H]酮色林的特异性结合。将利血平加入组织培养液中对这些配体的结合几乎没有影响。给大鼠每日服用氯丙嗪（33 - 36毫克/千克）长达12个月，可减少额叶皮质中[3H]酮色林的特异性结合位点数量（Bmax），但不改变[3H]WB 4101或[3H]可乐定与皮质膜的特异性结合。相比之下，用奥昔哌汀（6.3 - 7.3毫克/千克/天）、丁苯那嗪（6.0 - 6.7毫克/千克/天）或利血平（0.28 - 0.30毫克/千克/天）治疗可增加[3H]WB 4101特异性结合的Bmax，但不改变[3H]可乐定或[3H]酮色林的特异性结合。奥昔哌汀在与脑内α-肾上腺素能受体和5-HT2受体相互作用的能力方面与氯丙嗪相似。丁苯那嗪和利血平对突触后单胺受体几乎没有直接作用。然而，长期给药时，奥昔哌汀与丁苯那嗪和利血平一样，主要改变α1肾上腺素能受体，而氯丙嗪则影响5-HT2受体群体。
