Effect of different dosage regimens of a topical formulation of Hemantane on complete Freund`s adjuvant-induced nonspecific inflammation in rats

Abstract

The aim of the study was to evaluate the ability of different once-daily treatment regimens with N-(2-adamantyl) hexamethyleneimine hydrochloride (hemantane) topical gel vs. diclofenac topical gel to reduce nonspecific inflammation in rats induced with complete Freund’s adjuvant. Methods. Inflammation was induced by a subplantar injection of complete Freund’s adjuvant into the left hind paw of outbred rats. Edema of the left hind paw was measured. 5% hemantane gel (provided by the Laboratory of Finished Dosage Forms, V.V. Zakusov Institute of Pharmacology) and 1% diclofenac gel (produced by Hemofarm) were applied daily to the affected rat limb for 14 days. The experiment was performed in two stages. At the first stage, the drugs in the form of topical gels were applied to the left hind paw daily starting one day before the induction of inflammation. At the second stage, the topical gel formulations were applied daily starting two weeks after the induction of inflammation. At the first stage of the investigation, on day 4 after the injection of complete Freund’s adjuvant, coordination disorder of rats induced by the experimental pathology was evaluated using an Opto-Varimex actometer (Columbus Instruments, USA). Results. At the first stage of the study, hemantane gel significantly reduced edema of the foot and ankle joint of the left hind paw on days 3 and 7 after the induction of inflammation and was non-inferior to diclofenac gel. On day 14 after the injection of complete Freund’s adjuvant into the rat hind paw, the drugs had no significant effect on edema of the paw. On day 4 after the injection, the number of horizontal movements decreased by 34.03% as indicated by the Opto-Varimex actometer; 5% hemantane gel and 1% diclofenac gel improved coordination in rats by 52.35% and 45.72%, respectively. At the second stage of the study, 5% hemantane gel reduced foot edema in the model of inflammation after 7 and 14 days of treatment, whereas 1% diclofenac gel exerted no significant effect. Conclusion. Hemantane as a topical formulation reduces edema in outbred rats with nonspecific inflammation induced by the subplantar injection of complete Freund’s adjuvant into the left hind paw when applied daily, starting either one day before the induction of inflammation or two weeks after the complete Freund’s adjuvant administration, and its efficacy was not inferior to diclofenac as a topical formulation.