Ivanova Elena, Matyushkin Alexander, Sorokina Alexandra, Alexeeva Svetlana, Miroshkina Irina, Kachalov Kirill, Voronina Tatyana, Durnev Andrey
Laboratory of Psychopharmacology, FSBI Zakusov Institute of Pharmacology, Moscow, Russia.
Laboratory of Drug toxicology, FSBI Zakusov Institute of Pharmacology, Moscow, Russia.
Adv Pharm Bull. 2024 Mar;14(1):241-252. doi: 10.34172/apb.2024.002. Epub 2023 Jul 19.
N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund's Complete Adjuvant (FCA).
On day 14 after an FCA injection into the left hind paw, rats with contralateral hind paw edema were selected for further investigation (29/65). They were treated with 5% hemantane gel or 1% diclofenac gel applied locally to hind paws daily for 2 weeks starting 14 days after the FCA injection. Rats with arthritis were examined hind paw edema, hyperalgesia, and motor deficits; their body weight and hematological parameters were recorded. The rats were euthanized on day 28, followed by histological examination of the ankle joint (HE stain).
Rats with arthritis exhibited hind paw inflammation and hyperalgesia, motor deficits, changes of hematological parameters, reduced weight gain and spleen hypertrophy. Histological examination of the ankle joint revealed degenerative-dystrophic lesions of the cartilaginous tissue, proliferative inflammation of the synovium, edema and lymphocytic/macrophage infiltration of periarticular tissues. Hemantane gel reduced hind paw edema, pain, motor deficits and histological signs of inflammation; its effect was comparable to diclofenac gel.
Hemantane gel alleviates FCA-induced arthritis in rats, and its effect is comparable to diclofenac gel.
T细胞表达的N-甲基-D-天冬氨酸（NMDA）受体可调节T细胞增殖、细胞毒性以及细胞向趋化因子的迁移。多项研究表明NMDA受体拮抗剂具有抗炎作用。本研究比较了非竞争性低亲和力NMDA受体拮抗剂盐酸N-（2-金刚烷基）-六亚甲基亚胺（海曼坦）局部制剂（凝胶）与环氧化酶（COX）抑制剂双氯芬酸局部制剂（凝胶）对弗氏完全佐剂（FCA）诱导的大鼠关节炎的影响。
在左后爪注射FCA后第14天，选择对侧后爪出现水肿的大鼠进行进一步研究（29/65）。从FCA注射后14天开始，每天给它们的后爪局部涂抹5%海曼坦凝胶或1%双氯芬酸凝胶，持续2周。对患有关节炎的大鼠检查后爪水肿、痛觉过敏和运动功能障碍；记录它们的体重和血液学参数。在第28天对大鼠实施安乐死，随后对踝关节进行组织学检查（苏木精-伊红染色）。
患有关节炎的大鼠表现出后爪炎症、痛觉过敏、运动功能障碍、血液学参数变化、体重增加减少和脾脏肥大。踝关节组织学检查显示软骨组织出现退行性营养不良性病变、滑膜增生性炎症、水肿以及关节周围组织的淋巴细胞/巨噬细胞浸润。海曼坦凝胶减轻了后爪水肿、疼痛、运动功能障碍和炎症的组织学征象；其效果与双氯芬酸凝胶相当。
海曼坦凝胶可减轻FCA诱导的大鼠关节炎，其效果与双氯芬酸凝胶相当。
