Effects of Harmane, Norharman and Harmine on the Hot Plate- and Formalin-Induced Nociceptions in Mice

Background and Harmane, norharmane and harmine are b-carboline members of the family of Harmala,s alkaloids (Peganum harmala, Zygophillaceae). The b-carboline alkaloids bind to benzodiazepine site of the γ-aminobutyric acid type  (GÂBÂÂ) receptors as inverse. This finding suggest that the harmane, norharmane and harmine should be able to attenuate the hot plate-and formalin-induced nociceptions in mice. Ïn this study, the antinociceptive effects of harmane, norharmane and harmine in the mice of hot plate and formalin tests were assessed. Âll experiments were carried out on male BÂLB/Ç mice (20-25 g). Ïn the hot plate test, antinociceptive effects of drugs were assessed using a hot plate apparatus (Harvard, ÜK). The hot plate temperature thermostatically set at 52.5 ± 0.5 _Ç. The latency to licking or kicking of the fore or hind paws was recorded at various times after drug injection. Ân cut-off time of 45 s was imposed to avoid tissue damage. Ïn the formalin test, total time spent in licking injected paw was recorded in 5min intervals from 0-5min (as early phase) and 15-50 min (as late phase) after injection of formalin.  decrease in the duration of the time spent in licking showing antinociceptive response. Ïn the hot plate test, i.p. injection of harmane (5-20 mg/kg, 7 mice per group), norharmane (5-15 mg/kg, 7 mice per group) and harmine (10 and 15 mg/kg, 7 mice per group), significantly produced an antinociceptive effect. The antinociceptive effects of harmane, norharmane and harmine were antagonized by flumazenil (2 mg/kg, i.p.). Ïn the formalin test, i.p. injection of the doses of 2.5-5-10 mg/kg, harmane, norharmane and harmine significantly produced an antinociceptive effect. The antinociceptive effects of harmane, norharmane and harmine were antagonized by flumazenil (5 mg/kg, i.p.). Çonclusion: 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.