Diverse analgesic effects of novel benzimidazole derivatives
ORIGINAL STUDIES
Abstract
BACKGROUND: The development of novel analgesics is a critical priority due to the high prevalence of pain-related pathologies and the limitations of current treatments, which are often associated with undesirable side effects.
AIM: This study aimed to evaluate the analgesic properties of new imidazobenzimidazole (BIF-70 and BIF-72) derivatives through in vivo testing, compare their efficacy with previously studied compounds, and assess potential aversive effects.
MATERIALS AND METHODS: Experiments were conducted on mature rats sourced from the Rappolovo nursery (Leningrad Region). Analgesic activity was assessed using models of somatic, inflammatory, and neurogenic pain, following guidelines for preclinical studies. The animals were divided into 3 groups. Analgesic efficacy was tested using the Plantar Test. Acute inflammation was induced via the formalin hyperalgesia model. Neurogenic pain was modeled through sciatic nerve injury. Aversive effects were evaluated using the conditioned place avoidance test. Statistical analysis was performed using two-factor ANOVA.
RESULTS: The compounds demonstrated high analgesic activity, comparable to morphine. BIF-70 exhibited activity in both phases of inflammation, surpassing butorphanol in the first phase. BIF-72 showed no activity in the first phase but outperformed butorphanol in the second phase. In the neurogenic pain model Both compounds were less effective than gabapentin but comparable to morphine. In addition, BIF-70 induced a euphoric effect, increasing the time spent in the chamber associated with its administration. In contrast, BIF-72 showed no aversive or rewarding effects.
CONCLUSIONS: The study identified new analgesics with efficacy comparable to classical drugs in certain models.
Notably, these compounds lacked the aversive effects typically associated with kappa-opioid agonists, highlighting their potential as promising therapeutic candidates.
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