Anti-inflammatory and analgesic propertiesof SS-68 indole derivative

Authors

  • Saida K. Bogus Kuban State Medical University
  • Konstantin F. Suzdalev Southern Federal University
  • Aleksandr V. Uvarov Kuban State Medical University
  • Pavel A. Galenko-Yaroshevsky Kuban State Medical University
  • Vasil'ev Pavel M. Volgograd State Medical University
  • Dmitryy V. Vinakov Belgorod State National Research University
  • Nina V. Kiseleva Kuban State Medical University
  • Andrey N. Kochetkov Volgograd State Medical University
  • Aleksandr V. Kiselev Krasnodar branch of S.N. Fyodorov Eye Microsurgery Complex

Abstract

The experiments with rats show that when administered intravenously (5 mg/kg) and intragastrically (5, 10, 15 and 20 mg/kg), SS-68 compound exerts an antiinflammatory effect (AIE) on models of acute inflammation, caused by carrageenin and serotonin, and exerts no AIE in case of edema induced by complete Freund‘s adjuvant (CFA) and histamine, except for intragastric administration at a dose of 20 mg/kg.

By its antiphlogogenic effect in case of carrageenin and serotonin edemas, SS-68 is comparable to diclofenac (5, 10 and 15 mg/kg intragastrically) and indomethacin (10 mg kg intragastriccally), and exceeds piroxicam (20 mg/kg intragastrically). By reference to its therapeutic index (TI), in the first case SS-68 exceeds diclofenac, indomethacin and piroxicam 2.2, 15.6 and 5.6 times, and in the second case it exceeds them 1.8, 12.8 and 4.4 times, respectively.

In the mouse acetic writhing test, which reflects the predominant effect on κ (kappa)- opioid receptors, SS-68 when administered intraperitoneally at doses of 0.03, 0.06 and 0.12 mg/kg causes a dose-dependent decrease in the number of writhes by 40.0, 69.0 and 80.3%, respectively. Butorphanol, used for comparison in doses of 0.03, 0.12, 0.24, 0.48 and 0.96 mg/kg, exerts a dose-dependent analgesic effect (AE), with the number of writhes being 41.5, 52.4, 65.3, 71.1 and 80.6%, respectively. By its analgesic activity and TI, SS-68 exceeds butorphanol 1.9 and 2.7 times, respectively. Based on the results of the docking of affinity indicators for κ1-opioid receptors of SS-68, butorphanol (agonist-antagonist), as well as U-50488 compounds (selective agonist), it was established that, in accordance with the calculated values of the binding constant, the affinity in relation to SS-68 was 4.53 times higher than for butorphanol, and when compared with U-50488 it was 2.84 times lower. The suggestion is that AE of SS-68, like that of butorphanol, can be linked with both affinity for κ1-receptors and for other types of opioid receptors (mu, delta) and κ- receptor subtypes (κ2 or κ3).

Keywords:

SS-68indole derivative, diclofenac sodium, indomethacin, piroxicam, anti-inflammatory effect, carrageenin, serotonin, histamine, complete Freund's adjuvant, analgesic effect, kappa opioid receptors

Author Contribution

Saida K. Bogus, Kuban State Medical University

PhD in Medicine, Assistant Professor, Department of Pharmacology.

Konstantin F. Suzdalev, Southern Federal University

PhD in Chemistry, Associate Professor, Department of Chemistry of Natural and High-molecular Compounds, Faculty of Chemistry.

Aleksandr V. Uvarov, Kuban State Medical University

PhD in Medicine, Associate Professor, Department of Pharmacology.

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

Doctor of Medical Science, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Department of Pharmacology.

Vasil'ev Pavel M., Volgograd State Medical University

Doctor of Biology, Professor, Department of Pharmacology and Bioinformatics.

Dmitryy V. Vinakov, Belgorod State National Research University

Post-graduate student, Department of Pharmacology, Institute of Medicine.

Nina V. Kiseleva, Kuban State Medical University

6-year student, Faculty of General Medicine

Andrey N. Kochetkov, Volgograd State Medical University

Research technician, Department of Pharmacology and Bioinformatics.

Aleksandr V. Kiselev, Krasnodar branch of S.N. Fyodorov Eye Microsurgery Complex

PhD in Medicine, Head of the Laboratory for Tissue Preservation "Eye Bank".

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Published

30-12-2017

How to Cite

Bogus SK, Suzdalev KF, Uvarov AV, Galenko-Yaroshevsky PA, Pavel M. V, Vinakov DV, Kiseleva NV, Kochetkov AN, Kiselev AV (2017) Anti-inflammatory and analgesic propertiesof SS-68 indole derivative. Research Results in Pharmacology 3(4): 26–34

Issue

Section

Experimental Pharmacology

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