intrathecal

Ziconotide Acetate (107452-89-1 free base) (Prialt) 是一种镇痛剂，已用于治疗神经性和非神经性疼痛。 Ziconotide 通过与位于伤害感受通路初级传入神经元末端部分的 N 型钙通道结合起作用，因此通过有效的镇痛作用减少突触传递。

Adenosine A1 receptor activator T62 是腺苷 A1 受体的变构增强剂，有镇痛作用。

Levobupivacaine 是一种氨基酰胺类局麻药，属于n-alkylsubstituted pipecoloxylidide 家族。它是bupivacaine 的 S-对映异构体。

Inosine pranobex (Delimmun) 是一种免疫增强剂，它是一种广谱抗病毒剂，用于 HIV 感染。

L-AP4 (L-APB) monohydrate is a potent and specific agonist for the group III mGluRs, with EC50s of 0.13, 0.29, 1.0, 249 μM for mGlu4, mGlu8, mGlu6 and mGlu7 receptors, respectively[1][2]. L-AP4 (5-30 μg, intrathecal inhection 4-5 days) significantly increases the paw withdrawal threshold in response to application of von Frey filaments in eight nerve-ligated rats in a dose-dependent manner. Intrathecal administration of different doses of L-AP4 is not associated with any evident motor dysfunction[2].Intrathecal injection of 30 μg of L-AP4 does not significantly alter the paw withdrawal latency in these normal rats[2].Topical application of 5 to 50 μM L-AP4 to the spinal cord significantly inhibited the evoked response of neurons to touch, pressure, pinch, and von Frey filaments in a concentration-dependent fashion[2]. Animal Model: Rats.[2] [1]. Selvam C, et al. Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites. J Med Chem. 2018 Mar 8;61(5):1969-1989. [2]. Chen SR, et al. Distinct roles of group III metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats. J Pharmacol Exp Ther. 2005 Jan;312(1):120-6.

PA-8是一种小分子的的 PACAP I 型(PAC1)受体拮抗剂，有 选择性、有效性和口服活性。PA-8抑制PACAP 诱导的CREB 在PAC1-受体上的磷酸化，但对VPAC11或VPAC2受体无抑制作用。PA-8也抑制pacap 诱导的体外cAMP 水平升高(IC50 = 2 nM)和体内鞘内注射后pacap 诱导的厌恶反应和机械异位性痛。

Sec-O-Glucosylhamaudol (Hamaudol 3-glucoside) 是从滨海前胡中分离得到的一种天然产物，能够降低 μ 阿片受体的蛋白水平，可用于缓解疼痛的研究。它通过调节脂多糖刺激的 RAW264.7 细胞系中的 p38 丝裂原活化蛋白激酶具有抗炎作用。

Mafosfamide is a synthetic oxazaphosphorine derivative with antineoplastic properties. Mafosfamide alkylates DNA, forming DNA cross-links and inhibiting DNA synthesis. Although closely related to cyclophosphamide, mafosfamide, unlike cyclophosphamide, does not require hepatic activation to generate its active metabolite 4-hydroxy-cyclophosphamide; accordingly, mafosfamide is potentially useful in the intrathecal treatment of neoplastic meningitis.

Mafosfamide sodium is a synthetic oxazaphosphorine derivative with antineoplastic properties. Mafosfamide sodium alkylates DNA, forming DNA cross-links and inhibiting DNA synthesis. Although closely related to cyclophosphamide, Mafosfamide sodium, unlike cyclophosphamide, does not require hepatic activation to generate its active metabolite 4-hydroxy-cyclophosphamide; accordingly, Mafosfamide sodium is potentially useful in the intrathecal treatment of neoplastic meningitis.

K 41498 是一种针对皮质酮释放因子受体2α（CRF2α）和CRF2β的肽拮抗剂，其在表达人类受体的HEK293细胞中的Ki值分别为0.66和0.62 nM。它对CRF2α和CRF2β具有选择性，与CRF1相比（在表达人类受体的HEK293细胞中Ki值为425 nM）。K 41498 (1.84 µg/动物, 静脉注射) 能够阻止大鼠由于尿催肾上腺皮质激素引发的低血压。通过脊髓内给药，K 41498 (0.075-0.5 µmol/动物) 能降低完全弗氏佐剂引起的大鼠模型中机械性爪撤回阈值。

Tat-CBD3是一种抑制N型电压门控钙通道Cav2.2与collapsin response mediator protein 2 (CRMP2)之间的蛋白质-蛋白质相互作用的抑制剂。它还能抑制CRMP2与NMDA受体NR2B亚单位之间的蛋白质-蛋白质相互作用。在无细胞实验中，Tat-CBD3 (10 µM)能将Cav2.2-CRMP2相互作用抑制43%，并在免疫共沉淀实验中抑制NMDA受体NR2B亚单位-CRMP2相互作用。它能在初级大鼠背根神经节 (DRG) 神经元中减少约60%的电压诱导钙电流，并在初级大鼠海马神经元中减少谷氨酸诱导的胞内钙水平增加。Tat-CBD3 (20 mg/kg)在大鼠中脑动脉闭塞 (MCAO) 引发的脑缺血模型中减少梗死体积。鞘内给药Tat-CBD3 (20 µg/5 µl)可防止大鼠卡拉胶诱导的热敏感性。

Myr-Tat-CBD3是一种抑制N型电压门控钙通道Cav2.2与collapsin response mediator protein 2 (CRMP2)之间的蛋白-蛋白相互作用的抑制剂。在10 µM的浓度下，该化合物能够约81%地抑制Cav2.2-CRMP2相互作用，并在大鼠初级背根神经节(DRG)神经元中抑制钾诱导的钙流入（IC50约为2.8 µM）。在20 µM的浓度下，Myr-Tat-CBD3能抑制钙电流，但不影响钠电流，在初级DRG神经元中表现出这种特性。经过脊髓内给药，myr-Tat-CBD3（20 µg/5 µl）能够防止大鼠脚掌撤回潜伏期因carrageenan注射而减少。此外，Myr-Tat-CBD3减少大鼠因线索引起的寻求可卡因行为的复发。

LASSBio-873 是一种口服活性毒蕈碱胆碱能受体 (mAChR) 激动剂，并可穿过血脑屏障。它对急性疼痛和炎性疼痛具有有效的镇痛作用，其镇痛效果可被鞘内注射的 M2 受体拮抗剂 methoctramine 所抑制。