Naratriptan  (Synonyms: 那拉曲坦; GR-85548A)

Naratriptan is an orally active and selective 5-HT1B/1D receptor agonist. Naratriptan is peripherally active and has good oral bioavailability, inducing cranial artery vasoconstriction by activating 5-HT1B/1D receptors (EC₅₀=0.11 μM for dog basilar artery). Naratriptan also inhibits trigeminal nerve-mediated dural neurogenic plasma extravasation and reduces sterile inflammation. Naratriptan is mainly used in the research of acute migraine, targeting cranial vascular and neuroinflammatory mechanisms^[1][2][3][4].

Naratriptan 靶向人源重组 5-HT1B 和 5-HT1D 受体的 K_i 分别为 0.47 nM 和 0.69 nM，EC₅₀ 分别为 4.4 nM 和 23 nM；而对 5-HT1A 的 K_i=26 nM，EC₅₀=79 nM^[1]。
Naratriptan 靶向 5-HT1B、5-HT1D、5-HT1F 的 pK_i 分别为 8.7、8.3、8.1^[2]。
Naratriptan 可抑制猫来源调节呕吐的孤束核 (NTS) 细胞的放电反应，抑制率为 54%；该活性暗示了 Naratriptan 对三叉神经血管中 NTS 的抑制活性，可用于偏头痛的抑制研究^[2]。
Naratriptan 在狗离体基底动脉和大脑中动脉实验中引起浓度依赖性收缩，EC₅₀ 分别为 0.11 M 和 0.07 M^[3]。
Naratriptan 在人类离体心外膜冠状动脉实验中引起收缩，EC₅₀ 值为 0.17 μM；此时引起的最大收缩幅度为 5-HT 最大反应的 33%^[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Naratriptan (0.1-10 μg/kg；静脉插管；单次；电刺激三叉神经节前 15 min) 在大鼠硬脑膜神经源性炎症模型中抑制血浆蛋白外渗，ID₅₀ 为 4.1 μg/kg^[3]。
Naratriptan (10 mg/kg；口服；单次) 在雄性 Wistar 大鼠中的口服生物利用度为 71%。Naratriptan (0.5 mg/kg；口服；单次) 在比格犬中口服生物利用度为 95%^[3]。
与 μ-阿片受体激动剂的活性不同，Naratriptan [(10,30 μg/kg；鞘内注射；单次) 或 (10,30 mg/kg；皮下注射；单次)] 在小鼠甩尾实验和热板实验中均未增加小鼠的甩尾反应和热板反应的潜伏期。且 Naratriptan (10,30 mg/kg；皮下注射；单次) 在豚鼠和大鼠的爪压实验中，也未增加伤害性爪压阈值^[3]。
Naratriptan (10 mg/mL；静脉注射/离子电渗法；单剂量) 在猫三叉神经血管刺激模型中抑制三叉神经尾核神经元对矢状窦刺激的反应，且该作用可被 5-HT_1B/1D 受体拮抗剂 (5 mg/mL) SB224289 (HY-101105) 和 BRL15572 (HY-13200B) 逆转^[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

335.46

C₁₇H₂₅N₃O₂S

121679-13-8

固体

White to off-white

那拉曲坦；纳拉曲坦

Room temperature in continental US; may vary elsewhere.

• [1]. Rhoden E, et al. Anti-poliovirus activity of protease inhibitor AG-7404, and assessment of in vitro activity in combination with antiviral capsid inhibitor compounds. Antiviral Res. 2013 May;98(2):186-91.  [Content Brief]

  [2]. Hoskin KL, et al. The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat. Brain Res. 2004 Feb 13;998(1):91-9.  [Content Brief]

  [3]. Connor HE, et al. Naratriptan: biological profile in animal models relevant to migraine. Cephalalgia. 1997 May;17(3):145-52.  [Content Brief]

  [4]. Donaldson C, et al. The role of 5-HT1B and 5-HT1D receptors in the selective inhibitory effect of naratriptan on trigeminovascular neurons. Neuropharmacology. 2002 Mar;42(3):374-85.  [Content Brief]