Bachy A, Steinberg R, Santucci V, Fournier M, Landi M, Hamon M, Manara L, Keane P E, Soubrié P, Le Fur G
Sanofi Recherche, Toulouse, France.
Fundam Clin Pharmacol. 1993;7(9):487-97. doi: 10.1111/j.1472-8206.1993.tb00253.x.
SR 57746A (1-[2-(naphth-2-yl) ethyl]-4-(3-trifluoromethylphenyl)-1, 2, 5, 6 tetra-hydropyridine hydrochloride) binds competitively, and with high affinity (Ki = 2.0 +/- 0.7 nM) to 5-HT1A receptors from rat hippocampus in vitro, but has much less affinity for other 5-HT receptor subtypes (IC50 > 650 nM). SR 57746A produces a concentration-dependent inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal homogenates, with a maximal effect identical to that of 8-OH-DPAT, suggesting that SR 57746A behaves as a full agonist in this experimental model. SR 57746A potently displaces [3H]8-OH-DPAT binding to rat hippocampal membranes ex vivo, with an ID50 of 11.1 mg/kg po, 30 min after administration, and 2.8 mg/kg po, 2 h after administration. This effect of SR 57746A is long-lasting (at least 24 hours at 10 mg/kg po). SR 57746A does not modify the levels of 5-HT or DA in various brain areas, but decreases the concentrations of 5-HIAA, and increases those of DOPAC, HVA and 3-MT. Following i.v. administration, SR 57746A (0.095 to 0.25 mg/kg) inhibits the spontaneous firing of dorsal raphe neurones, but does not modify the activity of DA neurones in the substantia nigra or ventral tegmental area. Thus, SR 57746A is a potent, selective and full agonist at 5-HT1A receptors in vitro and vivo.
SR 57746A（1-[2-(萘-2-基)乙基]-4-(3-三氟甲基苯基)-1,2,5,6-四氢吡啶盐酸盐）在体外与大鼠海马体的5-HT1A受体竞争性结合，且亲和力高（Ki = 2.0±0.7 nM），但对其他5-HT受体亚型的亲和力则低得多（IC50>650 nM）。SR 57746A对大鼠海马体匀浆中福斯高林刺激的腺苷酸环化酶活性产生浓度依赖性抑制，最大效应与8-OH-DPAT相同，表明SR 57746A在该实验模型中表现为完全激动剂。SR 57746A能有效取代体内[3H]8-OH-DPAT与大鼠海马体膜的结合，口服给药后30分钟，ID50为11.1 mg/kg，给药后2小时为2.8 mg/kg。SR 57746A的这种作用持续时间长（口服10 mg/kg至少持续24小时）。SR 57746A不改变各脑区5-HT或DA的水平，但降低5-HIAA的浓度，并增加DOPAC、HVA和3-MT的浓度。静脉注射后，SR 57746A（0.095至0.25 mg/kg）抑制中缝背核神经元的自发放电，但不改变黑质或腹侧被盖区DA神经元的活性。因此，SR 57746A在体外和体内都是5-HT1A受体的强效、选择性和完全激动剂。
