Harmane hydrochloride is a benzodiazepine receptor inhibitor ( IC50 =7 μM), with IC50 values for mACh, Opioid Receptor, MAO-A/B, and α2-adrenergic receptor of 24 μM, 2.8 μM, 0.5 μM, 5 μM, and 18 μM, respectively. Harmane hydrochloride inhibits the I1 imidazoline receptor ( IC50 = 30 nM) to reduce blood pressure and has antidepressant, anti-anxiety, anticonvulsant, and analgesic effects. Harmane hydrochloride inhibits dopamine biosynthesis by decreasing tyrosine hydroxylase (TH) activity and enhancing L-DOPA-induced cytotoxicity in PC12 cells. Additionally, Harmane hydrochloride can increase the mutagenic effect induced by 2-acetylaminofluorene (AAF) [1] [2] [3] [4] [5] [6].
In Vivo, Harman (0-12.5mg/kg, i.v., single dose) has an ED50 of 3.6 mg/kg for convulsant activity in rats. Its anticonvulsant effect lasts for a short time and delays the reaction time to pain[1]. Harman (0.01-1 nM, injected into rostralventrolateral medulla, single dose) caused a decrease in blood pressure in rats[2]. Harman (2.5-10 mg/kg, i.p., single dose) had anxiolytic and antidepressant effects in rats[5].
In Vitro, Harmane hydrochloride also inhibits haloperidol and serotonin, with IC50 values of 163 μM and 101 μM, respectively[1]. The IC50 of Harmane hydrochloride for benzodiazepine receptor flunitrazepam is 7 μM, the IC50 for the opioid receptor is 2.8 μM, and in the presence of 50 mM sodium ions, the IC50 for the opioid receptor is 42 μM, and the IC50 for spiropyrinol and serotonin is 163, 101 μM[1]. The IC50 of Harmane hydrochloride for I1 imidazoline receptor is 30 nM), and the IC50 for α2-adrenergic receptor is 18 μM[2]. Harmane hydrochloride (1 μM) increases the mutagenicity of AAF to Salmonella typhimurium TA98 by three times in the presence of an S-9 mixture (containing 4 μM NADH and NADPH per ml but no NADP); in the absence of S-9, it increases the mutagenicity of N-acetyloxy AAF by 2.5 times[4]. Harmane hydrochloride (5-25 μM, 0-72 h) reduced the dopamine content in PC12 cells (IC50 is 21.2 μM) in a concentration-dependent manner and could reduce the dopamine content induces by L-DOPA[6]. Harmane hydrochloride (20 μM, 0-72 h) inhibits the activity of tyrosine hydroxylase (TH) in PC12 cells at 24 h and restores it to normal levels at 72 h; it inhibits the expression of TH mRNA at 6 h and restores it at 48 h[6]. Harmane hydrochloride (20μM, 30min) reduces the intracellular cyclic AMP level and intracellular calcium ion concentration in PC12 cells[6]. Harmane hydrochloride (80-150μM, 24-48h) exhibits cytotoxicity and induces cell death[6].
References:
[1]. W E Müller, et al. On the neuropharmacology of harmane and other beta-carbolines. Pharmacol Biochem Behav. 1981 May;14(5):693-9.
[2]. Musgrave IF, et, al. Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors. Br J Pharmacol. 2000 Mar;129(6):1057-9.
[3]. Glover V, et, al. β-Carbolines as selective monoamine oxidase inhibitors:In vivo implications
[4]. https://pubmed.ncbi.nlm.nih.gov/345280/
[5]. E D Louis, et al. Harmane induces anxiolysis and antidepressant-like effects in rats. Ann N Y Acad Sci. 2005 Aug 9;65(3):391-6.
[6]. Yoo Jung Yang, et al. Effects of harman and norharman on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. Eur J Pharmacol. 2008 Jun 10;587(1-3):57-64.
In Vivo, Harman (0-12.5mg/kg, i.v., single dose) has an ED50 of 3.6 mg/kg for convulsant activity in rats. Its anticonvulsant effect lasts for a short time and delays the reaction time to pain[1]. Harman (0.01-1 nM, injected into rostralventrolateral medulla, single dose) caused a decrease in blood pressure in rats[2]. Harman (2.5-10 mg/kg, i.p., single dose) had anxiolytic and antidepressant effects in rats[5].
In Vitro, Harmane hydrochloride also inhibits haloperidol and serotonin, with IC50 values of 163 μM and 101 μM, respectively[1]. The IC50 of Harmane hydrochloride for benzodiazepine receptor flunitrazepam is 7 μM, the IC50 for the opioid receptor is 2.8 μM, and in the presence of 50 mM sodium ions, the IC50 for the opioid receptor is 42 μM, and the IC50 for spiropyrinol and serotonin is 163, 101 μM[1]. The IC50 of Harmane hydrochloride for I1 imidazoline receptor is 30 nM), and the IC50 for α2-adrenergic receptor is 18 μM[2]. Harmane hydrochloride (1 μM) increases the mutagenicity of AAF to Salmonella typhimurium TA98 by three times in the presence of an S-9 mixture (containing 4 μM NADH and NADPH per ml but no NADP); in the absence of S-9, it increases the mutagenicity of N-acetyloxy AAF by 2.5 times[4]. Harmane hydrochloride (5-25 μM, 0-72 h) reduced the dopamine content in PC12 cells (IC50 is 21.2 μM) in a concentration-dependent manner and could reduce the dopamine content induces by L-DOPA[6]. Harmane hydrochloride (20 μM, 0-72 h) inhibits the activity of tyrosine hydroxylase (TH) in PC12 cells at 24 h and restores it to normal levels at 72 h; it inhibits the expression of TH mRNA at 6 h and restores it at 48 h[6]. Harmane hydrochloride (20μM, 30min) reduces the intracellular cyclic AMP level and intracellular calcium ion concentration in PC12 cells[6]. Harmane hydrochloride (80-150μM, 24-48h) exhibits cytotoxicity and induces cell death[6].
References:
[1]. W E Müller, et al. On the neuropharmacology of harmane and other beta-carbolines. Pharmacol Biochem Behav. 1981 May;14(5):693-9.
[2]. Musgrave IF, et, al. Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors. Br J Pharmacol. 2000 Mar;129(6):1057-9.
[3]. Glover V, et, al. β-Carbolines as selective monoamine oxidase inhibitors:In vivo implications
[4]. https://pubmed.ncbi.nlm.nih.gov/345280/
[5]. E D Louis, et al. Harmane induces anxiolysis and antidepressant-like effects in rats. Ann N Y Acad Sci. 2005 Aug 9;65(3):391-6.
[6]. Yoo Jung Yang, et al. Effects of harman and norharman on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. Eur J Pharmacol. 2008 Jun 10;587(1-3):57-64.