| Abstrakt: |
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 (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 1-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 forκ1-receptors and for other types of opioid receptors (mu, delta) and κ-receptor subtypes (κ2 or κ3). [ABSTRACT FROM AUTHOR] |
