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Adv Pharm Bull. 2024;14(1): 241-252.
doi: 10.34172/apb.2024.002
  Abstract View: 463
  PDF Download: 302

Research Article

Low-Affinity NMDA Receptor Antagonist Hemantane in a Topical Formulation Attenuates Arthritis Induced by Freund’s Complete Adjuvant in Rats

Elena Ivanova 1* ORCID logo, Alexander Matyushkin 1, Alexandra Sorokina 2, Svetlana Alexeeva 2, Irina Miroshkina 2, Kirill Kachalov 2, Tatyana Voronina 1, Andrey Durnev 2

1 Laboratory of Psychopharmacology, FSBI Zakusov Institute of Pharmacology, Moscow, Russia.
2 Laboratory of Drug toxicology, FSBI Zakusov Institute of Pharmacology, Moscow, Russia.
*Corresponding Author: Elena Ivanova, Email: ivanovae@academpharm.ru

Abstract

Purpose: 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).

Methods: 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).

Results: 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.

Conclusion: Hemantane gel alleviates FCA-induced arthritis in rats, and its effect is comparable to diclofenac gel.

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Submitted: 08 Jun 2022
Revision: 12 Apr 2023
Accepted: 14 Jul 2023
ePublished: 19 Jul 2023
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