Harmane-d1 是 Harmane 的氘代物。Harmane，一种 β-咔啉生物碱 (BCA)，是有效的神经毒素，可引起严重的动作震颤和精神病学表现。Harmane 对 I1 咪唑啉受体 (I1-Imidazoline receptor, IC50=30 nM) 的选择性是对 α2-肾上腺素受体 (IC50=18 μM) 的 1000 倍。Harmane 还是有效和选择性的单胺氧化酶抑制剂 (对 MAO A/B 的 IC50 值分别为 0.5 μM 和 5 μM)。
Harmane-d1 is the deuterium labeled Harmane. Harmane, a β-Carboline alkaloid (BCA), is a potent neurotoxin that causes severe action tremors and psychiatric manifestations. Harmane shows 1000-fold selectivity for I1-Imidazoline receptor (IC50=30 nM) over α2-adrenoceptor (IC50=18 μM). Harmane is also a potent and selective inhibitor of monoamine oxidase (MAO) (IC50s=0.5 and 5 μM for human MAO A/B, respectively)[1][2][3][4].
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Louis ED, et, al. Blood harmane concentrations and dietary protein consumption in essential tremor. Neurology. 2005 Aug 9;65(3):391-6.
[3]. 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.
[4]. Glover V, et, al. β-Carbolines as selective monoamine oxidase inhibitors:In vivo implications
[5]. Umezawa K, et, al. Comutagenic effect of norharman and harman with 2-acetylaminofluorene derivatives. Proc Natl Acad Sci U S A. 1978 Feb;75(2):928-30.
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