[Effects of harmane, norharmane and harmine on writhing behavior induced by acetic acid in mice]

The beta-carbolines harmane, harmine and norharmane are the members of Harmala,s alkaloids group [Peganum harmala, Zygophillaceae]. The beta-carboline alkaloids adjoined to benzodiazepine site of the gamma-aminobutyric acid type A [GABA[A]]. These alkaloids also inhibited cyclooxygenase and lipoxygenase activities. These findings showed that the beta-carbolines should be able to reduce writhing nociception induced by acetic acid- in mice. To assess the effects of acute treatment with harmane, norharmane and harmine on the writhing induced by acetic acid in mice. The experiments were carried out on male BALB/C mice [20-25g]. Intraperitoneal [I.p] injection of acetic acid [0.6%] was performed in order to cause writhing behavior. This behavior was recorded by direct observation for a 30-minutes period. Decrease of writhing count is indicative of an anti-nociception. In order to avoid the possibility of a physicochemical interaction between them, Drugs were administered on opposite sides of peritoned. Intraperitoneal [I.p] injection of Harmane [5-20mg/kg] on 6-9 mice, norharmane [5-15mg/kg] on 8-9 mice and harmine [10-15mg/kg] on 8-9 mice in per group decreased the writhing behavior significantly [P<0.0001, P<0.0003 and P<0.0016, respectively]. The inhibitory effects of the mentioned drugs were antagonized by flumazenil [2 mg/kg]. Effects of harmane, norharmane and harmine on writhing response may be mediated through an inverse agonistic mechanism located in the benzodiazepine receptors

[Effects of harmane, norharmane and harmine on apomorphine-induced pecking behavior in chick]

Beta-carboline alkaloids, also known as harmala's alkaloids have a wide spectrum of pharmacological actions including a stimulatory action on release of dopamine and other catecholamines in several brain regions and an inhibitory action on monoamine oxidase [MAO]. These findings suggest that beta-carbolines should alleviate at least some of the dopaminergic stereotyped behaviors. The purpose of present study is to determine the effects of beta-carbolines harmane, norharmane and harmine on apomorphine-induced pecking behavior in chick. All experiments were carried out on male/female chicks [40-60 g]. The modulatory effects of beta-Carbolines on stereotyped behavior were assessed using the pecking behavior induced by apomorphine. Subcutaneous [s.c.] injection of apomorphaine [0.025 mg/kg, mixed agonist of dopamine D1/D2 receptors] induced pecking. The pecking response was counted by direct observation and recorded for a 40-minute period. S.C. injection of harmane [2.5-10 mg/kg] and harmine [1.25-5 mg/kg] significantly decreased the pecking behavior induced by apomorphine [0.25 mg/kg]. The norharmane [2.5-15 mg/kg, i.p.] response was biphasic. The inhibitory effects of harmane, norharmane and harmine were blocked by flumazenil [5 mg/kg, i.e., 30 minutes before the test] or reserpine [5 mg/kg, i.e., 18 hours before the test]. Results suggest that the modulatory effect of harmane, norharmane and harmine on the pecking behavior may be mediated through an inverse agonistic/monoaminergic mechanism

[Evaluation of antidepressant activities of harmane, norharman and harmine in mice]

It has been reported that, the [R]-carboline alkaloids of peganum harmala seeds have a stimulatory action on serotonin and catecholamines releases in different brain regions. In addition, one of the most important pharmacological effects demonstrated for [R]- carbolines is a revesible inhibitory action on MAO-A. These findings suggest that - carbolines, should alleviate at least some of the signs of depression. The purpose of present study is to determine the antidepressant activity of [R]-carbolines harmane, norharmane and harmine. All experiments were carried out on male Swiss-Webster mice [25-30g]. The antidepressant activities of the [R]-carbolines were assessed using the forced swim test. This test is the most widely used tool for antidepressant activity preclinically. In this test, mice were placed into a cylinderical glass [25 cm height, 12 cm in diameter] containing a column of 15 cm of water at 25 +/- 1 [o]C. After 30 min of the-carbolines injections, the mice were subjected to forced swimming test for 8 min and their immobility time was recorded. Intraperitoneal [i.p.] injections of harmane [5-15 mg/kg], norharmane [2.5-10 mg/kg] and harmine [5-15 mg/kg] significantly decreased the immobility time in the mouse forced swim test. The inhibitory effects of harmane, norharmane and harmine were antagonized by flumazenil [5 mg/kg, i.p.] but not by reserpine [5 mg/kg, i.p., 18 h before test]. The results suggest that the antidepressant activities of harmane, norharmane and harmine may be mediated through an inverse agonistic mechanism