Analgesic activity of a new cannabinoid CB₁ receptor modulator

Aim. To study the analgesic activity, the effect on motor functions, and the potential ulcerogenic effect of a new 2H-chromene derivative, a cannabinoid CB₁ receptor modulator (code name – CHR).

Materials and methods. The analgesic activity of the CHR compound was studied when injected intragastrically at an effective dose of 5 mg / kg in mouse models of acute chemogenic pain (formalin test), acute visceral pain (the acetic acid-induced writhing test), and thermal nociception (hot plate test and tail-flick test). It was compared to the effect of tramadol and morphine or diclofenac sodium at doses of 20, 4 or 10 mg / kg, respectively. The effect of a single intragastric injection of the CHR compound at a dose of 5 mg / kg on motor activity was evaluated in the open field test. The potential ulcerogenic effect of the CHR compound at a dose of 5 mg / kg with repeated intragastric administration was compared with the effect of diclofenac sodium at a dose of 10 mg / kg.

Results. With subplantar administration of formalin to mice, the 2H-chromene derivative reduced the number of pain reactions by 43–63% (p < 0.05). With intraperitoneal administration of acetic acid to mice, it reduced the number of writhing responses by 50% and had the same analgesic effect as diclofenac sodium and tramadol. In the hot plate test, the CHR compound increased the latency time to painful stimuli by 34% (p < 0.05). In the tailflick test, it increased the latency time to painful thermal sensations by 32% (p < 0.05). The CHR compound at an effective dose of 5 mg / kg did not change the motor activity of mice in the open field test and did not cause the formation of erosions and ulcers in the gastric mucosa when administered repeatedly to rats.

Conclusion. The 2H-chromene derivative CHR at an effective dose of 5 mg / kg has a pronounced analgesic effect in mouse models of chemogenic, visceral, and thermal pain, which is as strong as that of tramadol, morphine, and diclofenac sodium used at effective doses. The CHR compound at an effective dose does not inhibit motor functions and does not have an ulcerogenic effect.

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