Comparative characteristics of new benzimidazole derivatives with potential analgesic properties
INNOVATIVE PHARMACOLOGY
Abstract
Introduction. The development of novel highly effective analgesics represents a critical objective due to the high prevalence of pain syndrome as a component of various pathological conditions, which significantly impairs patients’ quality of life.Aim.The study aimed to investigate the duration of action of two novel opioid analgesics, determine their median lethal (LD50) and median effective (ED50) doses, and calculate their therapeutic indices.Materials and methods. The analgesic activity was assessed using the Tail Flick test. The ED50was determined based on the results of an additional Tail Flick assay. To estimate the LD50, the test compounds were administered at doses exceeding the previously determined ED50by more than 100-fold. The therapeutic index was calculated as the ratio of LD50to ED50.Results.For compound BIF-70, the ED50was 0.7854 mg/kg, the LD50was 304.3 mg/kg, and the therapeutic index was 387.45. For
BIF-72, the ED50was 0.5852 mg/kg, the LD50was 331.4 mg/kg, and the therapeutic index was 566.3. The duration of analgesic action for both compounds was at least 150 minutes at doses ranging from 1 to 10 mg/kg.Discussion.The duration of action of the studied compounds was comparable to that of classical opioid analgesics. The LD50values for both substances were consistent with those of conventional opioids. Notably, the therapeutic indices of BIF-70 and BIF-72 significantly exceeded that of morphine, though they remained lower than that of butorphanol.Conclusions.Both compounds demonstrate promising pharmacological profiles as potential opioid analgesics and warrant further preclinical investigation.
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