87760-53-0
87760-53-0 结构式
基本信息
3A,4,7,7A-六氢-2-(4-(4-(2-嘧啶基)-1-哌嗪基)丁基)-4,7-甲桥-1H-异吲哚-1,3(2H)-二酮
(3ΑΑ,4Β,7Β,7ΑΑ)-六氢-2-[4-[4-(2-嘧啶基)-1-哌嗪基]丁基]-4,7-亚甲基-1H-异吲哚-1,3(2H)-二酮
REL-(3AR,4S,7R,7AS)-2-(4-(4-(嘧啶-2-基)哌嗪-1-基)丁基)六氢-1H-4,7-甲桥异吲哚-1,3(2H)-二酮
87760-53-0
TANDOSPIRONE
(3aR,4S,7R,7aS)-rel-
Tandospirone (SM3997)
Tandospirone [inn:ban]
TANDOSPIRONE USP/EP/BP
Tandospirone hydrochloride
3a,4,7,7a-Hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-4,7-methano-1H-isoindole-1,3(2H)-dione
(1R*,2S*,3R*,4S*)-N-(4-(4-(2-Pyrimidinyl)-1-piperazinyl)butyl)-2,3-norbornanedicarboximide citrate salt
物理化学性质
柠檬酸坦度螺酮(Tandospirone Citrate)：C2Lh29N5O2?C6H8O7。[112457-95-1]。
盐酸坦度螺酮(Tandospimne Hydrochloride)：C2lH29N5O2?HCl。从异丙醇结晶，熔点227～229℃。
常见问题列表
（1）损害言语记忆 激动双侧海马突触后膜的5-HT1A受体→激动G蛋白→打开内流K +通道→K +内流→神经元抑制,损害清晰言语记忆。
（2）致失眠 坦度螺酮在杏仁核基底核群能激活γ-氨基丁酸(GABA)神经元突触前膜上的5-HT1A受体,抑制GABA释放,可引起失眠(0.1%～1%)和噩梦(<1%)。
（3）降血压 坦度螺酮激动5-HT受体,有中枢性降血压作用,降血压时扩血管,扩血管可使血浆成分渗入组织间隙,引起浮肿,浮肿压迫神经末梢,可致四肢发麻。 （4）高催乳素血症 坦度螺酮激动5-HT1A受体,从而刺激催乳素分泌。已有坦度螺酮引起男子女性型乳房的报告。
2.抑制单胺氧化酶 坦度螺酮抑制单胺氧化酶,导致单胺代谢受阻,引起单胺(包括5-HT、NE和DA)的突触水平升高,单胺水平升高可引起一系列不良反应。
（1）拟5-HT能效应 当突触5-HT能增加时,可引起锥体外系反应、恶心、厌食和腹泻。
（2）拟NE能效应 当突触NE水平增加时,类似交感神经兴奋,在神经系统可引起失眠、噩梦、头痛(0.1%～1%)、眩晕(0.1%～1%)、头昏和震颤(<1%);在消化系统可引起口干、恶心(0.9%)、厌食(0.7%)、胃胀、腹胀和便秘,在心血管系统可引起心悸、心动过速(0.1%～1%)和多汗(发汗或盗汗);并因代谢增加而引起胸红和灼热感。
3.弱抗DA能效应 坦度螺酮有弱抗DA能效应,服后可出现类帕金森氏病样症状,如果肋间肌肌张力增加,可解释胸闷症状(0.1%～1%)。坦度螺酮联合氟哌啶醇可能加强锥体外系反应。
|
5-HT 1A Receptor 27 nM (Ki) |
Tandospirone is approximately two to three orders of magnitude less potent at 5-HT
2
, 5-HT
1C
, α1-adrenergic, α2-adrenergic and dopamine D1 and D2 receptors (K
i
values ranging from 1300 to 41000 nM) than 5-HT
1A
.
Tandospirone is essentially inactive at 5-HT
1B
receptors; 5-HT uptake sites; beta-adrenergic, muscarinic cholinergic, and benzodiazepine receptors.
Tandospirone activats postsynaptic 5-HT
1A
receptor coupled with G-protein (G
i/o
), resulting in inhibition of protein kinase A (PKA)-mediated protein phosphorylation and neuronal activity.
Tandospirone (10-80 mg/kg; i.p.) inhibits freezing behavior in the conditioned fear stress-induced freezing behavior rat model.
Tandospirone exhibits the anxiolytic effect dependent on the plasma concentration of at 0.5 hours but not 4 hours.
| Animal Model: | Seven-week-old male Sprague-Dawley rats (260-300 g), conditioned fear stress-induced freezing behavior rat model |
| Dosage: | 10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg |
| Administration: | Intraperitoneal injection |
| Result: | Inhibited freezing behavior in a dose-dependent manner. |