اثر هارمان، نورهارمان و هارمین بر درد القاء شده با صفحه داغ و فرمالین در موش

Background and purpose: Harmane, norharmane and harmine are -carboline members of the family of Harmalas alkaloids (Peganum harmala, Zygophillaceae). The -carboline alkaloids bind to benzodiazepine site of the γ-aminobutyric acid type A (GABAA) receptors as inverse agonists. This finding suggests that the harmane, norharmane and harmine might attenuate the hot-plate and formalin-induced nociceptions in mice. This study assessed the antinociceptive effects of harmane, norharmane and harmine in the mice used in hot-plate and formalin tests. Materials and methods: The experiment was carried out on male BALB/C mice (20-25 g). In the hot-plate test, antinociceptive effects of drugs were assessed using a hot plate apparatus (Harvard, UK). The hot-plate temperature was thermostatically set at 52.5 ±5 °C. The latency to licking or kicking of the fore or hind paws was recorded at various times after drug injection. To avoid tissue damage a cut-off time of 45 seconds was imposed. In the formalin test, total time spent licking injected paw was recorded in 5 min intervals from 0-5 min (as early phase) and 15-50 min (as late phase) after injection of formalin. A decrease in the duration of the time spent licking indicated an antinociceptive response. Results: In the hot-plate test i.p. injection of harmane (5-20 mg/kg, seven mice per group), norharmane (5-15 mg/kg, seven mice per group) and harmine (10 and 15 mg/kg, seven mice per group), led to a significant antinociceptive effect. The antinociceptive effects of harmane, norharmane and harmine were antagonized by flumazenil (2 mg/kg, i.p.) and naloxone (5mg/kg, i.p.). In the formalin test, i.p. injection of the doses of 2.5-5-10 mg/kg, harmane, norharmane and harmine resulted in a significant antinociceptive effect. The antinociceptive effects of harmane, norharmane and harmine were antagonized by flumazenil (5 mg/kg, i.p.). Conclusion: The results suggest that the antinociceptive effects of harmane, norharmane and harmine may be mediated through an inverse agonistic mechanism located in the benzodiazepine receptors.