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Objective: To identify the phytochemical constituents of Peganum harmala L. (P. harmala) seeds extract by gas chromatography-mass spectrometer (GC-MS) and evaluate their antidepressant activity. Methods: The seeds extract was analyzed by GC-MS to identify their major chemical compounds. The antidepressant activity of P. harmala was demonstrated using the forced swim test and the adrenocorticotropic hormone analysis. After oral administration of the seeds extract and diazepam in rats, the immobility time in the forced swim test was measured and the defecation rate was estimated for all rats. Results: GC-MS analysis showed the presence of indole alkaloids (β-carboline), for exmaple harmaline (48.009%), harmine (38.440%), tetrahydroharmine (8.513%), tetrahydroharman (0.061%) and 6-methoxytetrahydro-1-norharmanone (0.057%) were present in the extract. The results showed that the P. harmala extract (100 mg/kg and 300 mg/kg) were able to reduce the immobility time (80.20 ± 9.01, 46.80 ± 8.53; P < 0.001), the adrenocorticotropic hormone rate (131.33 ± 12.72, 49.72 ± 13.03; P < 0.001) and the defecation rate (1.400 ± 1.342, 0.600 ± 0.548; P < 0.01), respectively. Conclusions: This indicates that the seeds extract can correct the depression and reach the normal state of the treated animals. The results demonstrated that seeds represented a source of indole alkaloids (harmaline, harmine and tetrahydroharmine).

There is a general consensus in dentistry that successful local anesthesia is frequently difficult in habitual drinkers and alcoholic patients. Neuro-active tetrahydroharmans increase in human body fluids and tissues by consuming alcoholic beverages. To understand such reduced anesthetic efficacy by the drug interaction hypothesis, we studied the influences of drinking-related tetrahydroharmans on membrane fluidization as one of local anesthetic mechanisms. Liposomal membranes prepared with phosphatidylcholine and cholesterol were treated with lidocaine and different tetrahydroharmans separately and in combination, followed by measuring fluorescence polarization to determine their induced changes in membrane fluidity. In contrast to 0.1–2 mg/mL lidocaine, tetrahydroharmans decreased the fluidity of membrane preparations at ∼25 μg/mL with the potency being 1,2,3,4-tetrahydroharman ≫ 1,2,3,4-tetrahydronorharman. 1,2,3,4-Tetrahydroharman counteracted the membrane-fluidizing effects of 1 mg/mL lidocaine at physiologically relevant 0.25–2.5 ng/mL, whereas neither its 6-hydroxyl nor 7-hydroxyl metabolite did at 25–200 ng/mL. Such counteraction at a membrane lipid level may be responsible for the reduction of local anesthetic efficacy in drinkers because 1,2,3,4-tetrahydroharman increases in vivo by ingesting alcoholic beverages.