87760-53-0
87760-53-0 結(jié)構(gòu)式
基本信息
3A,4,7,7A-六氫-2-(4-(4-(2-嘧啶基)-1-哌嗪基)丁基)-4,7-甲橋-1H-異吲哚-1,3(2H)-二酮
(3ΑΑ,4Β,7Β,7ΑΑ)-六氫-2-[4-[4-(2-嘧啶基)-1-哌嗪基]丁基]-4,7-亞甲基-1H-異吲哚-1,3(2H)-二酮
REL-(3AR,4S,7R,7AS)-2-(4-(4-(嘧啶-2-基)哌嗪-1-基)丁基)六氫-1H-4,7-甲橋異吲哚-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
物理化學(xué)性質(zhì)
檸檬酸坦度螺酮(Tandospirone Citrate)：C2Lh29N5O2?C6H8O7。[112457-95-1]。
鹽酸坦度螺酮(Tandospimne Hydrochloride)：C2lH29N5O2?HCl。從異丙醇結(jié)晶，熔點(diǎn)227～229℃。
常見問題列表
（1）損害言語記憶 激動雙側(cè)海馬突觸后膜的5-HT1A受體→激動G蛋白→打開內(nèi)流K +通道→K +內(nèi)流→神經(jīng)元抑制,損害清晰言語記憶。
（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)神經(jīng)元突觸前膜上的5-HT1A受體,抑制GABA釋放,可引起失眠(0.1%～1%)和噩夢(<1%)。
（3）降血壓 坦度螺酮激動5-HT受體,有中樞性降血壓作用,降血壓時擴(kuò)血管,擴(kuò)血管可使血漿成分滲入組織間隙,引起浮腫,浮腫壓迫神經(jīng)末梢,可致四肢發(fā)麻。 （4）高催乳素血癥 坦度螺酮激動5-HT1A受體,從而刺激催乳素分泌。已有坦度螺酮引起男子女性型乳房的報告。
2.抑制單胺氧化酶 坦度螺酮抑制單胺氧化酶,導(dǎo)致單胺代謝受阻,引起單胺(包括5-HT、NE和DA)的突觸水平升高,單胺水平升高可引起一系列不良反應(yīng)。
（1）擬5-HT能效應(yīng) 當(dāng)突觸5-HT能增加時,可引起錐體外系反應(yīng)、惡心、厭食和腹瀉。
（2）擬NE能效應(yīng) 當(dāng)突觸NE水平增加時,類似交感神經(jīng)興奮,在神經(jīng)系統(tǒng)可引起失眠、噩夢、頭痛(0.1%～1%)、眩暈(0.1%～1%)、頭昏和震顫(<1%);在消化系統(tǒng)可引起口干、惡心(0.9%)、厭食(0.7%)、胃脹、腹脹和便秘,在心血管系統(tǒng)可引起心悸、心動過速(0.1%～1%)和多汗(發(fā)汗或盜汗);并因代謝增加而引起胸紅和灼熱感。
3.弱抗DA能效應(yīng) 坦度螺酮有弱抗DA能效應(yīng),服后可出現(xiàn)類帕金森氏病樣癥狀,如果肋間肌肌張力增加,可解釋胸悶癥狀(0.1%～1%)。坦度螺酮聯(lián)合氟哌啶醇可能加強(qiáng)錐體外系反應(yīng)。
|
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. |