Clorgyline (hydrochloride) is an irreversible, potent and selective inhibitor of monoamine oxidase (MAO) A, with Ki values of 0.054 and 58μM for MAO-A and MAO-B, and IC50 values of 0.0012 and 1.9μM, respectively[1, 2]. MAO is responsible for the regulation and metabolism of major monoamine neurotransmitters such as serotonin (5-HT), norepinephrine (NE) and dopamine (DA)[3]. Clorgyline (hydrochloride) has little effect on the content of conjugated dopamine in rat striatal slices[4].
In vivo, Clorgyline (hydrochloride) (1.5mg/kg/day) was intraperitoneally injected into Huntington's disease mice for 21 days, which inhibited the activity of monoamine oxidase A (MAO-A) in the cortical tissue of mice by about 90%, significantly increased the levels of neurotransmitters 5-HT and NE in the striatum, improved anxiety-like phenotypes, and reduced depressive-like behaviors[5]. Treatment of rats with Clorgyline (hydrochloride) (2mg/kg/day) for 28 days increased the rats' nicotine intake[6].
References:
[1] Rullo M, La Spada G, Catto M, et al. Monoamine Oxidase Inhibition for the Treatment of Neurodegenerative Diseases: Rationale, Assay Methodologies, and Reference Compounds[M]//Methods in Neurodegenerative Disease Drug Discovery. New York, NY: Springer US, 2024: 137-150.
[2] Abdelhafez O M, Amin K M, Ali H I, et al. Synthesis of new 7-oxycoumarin derivatives as potent and selective monoamine oxidase A inhibitors[J]. Journal of Medicinal Chemistry, 2012, 55(23): 10424-10436.
[3] Naoi M, Maruyama W, Shamoto-Nagai M. Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis[J]. Journal of Neural Transmission, 2018, 125: 53-66.
[4] Tyce G M, Rorie D K. Conjugated dopamine in superfusates of slices of rat striatum[J]. Journal of Neurochemistry, 1982, 39(5): 1333-1339.
[5] Garcia-Miralles M, Ooi J, Bardile C F, et al. Treatment with the MAO-A inhibitor clorgyline elevates monoamine neurotransmitter levels and improves affective phenotypes in a mouse model of Huntington disease[J]. Experimental neurology, 2016, 278: 4-10.
[6] Guillem K, Vouillac C, Azar M R, et al. Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats[J]. European Journal of Neuroscience, 2006, 24(12): 3532-3540.
Clorgyline (hydrochloride)是一种不可逆、强效和选择性单胺氧化酶（MAO）A 抑制剂，对MAO-A和MAO-B的Ki值分别为0.054和58μM，IC50值分别为 0.0012和1.9μM[1, 2]。MAO负责主要单胺神经递质如5-羟色胺（5-HT）、去甲肾上腺素（NE）和多巴胺（DA）的调节和代谢[3]。Clorgyline (hydrochloride)对大鼠纹状体切片中共轭多巴胺的含量影响不大[4]。
在体内，Clorgyline (hydrochloride)（1.5mg/kg/day）通过腹腔注射治疗亨廷顿病小鼠21天，抑制了小鼠皮质组织中单胺氧化酶A（MAO-A）的活性约90%，显著升高了纹状体内神经递质5-HT和NE水平，改善了焦虑样表型，减少了抑郁样行为[5]。Clorgyline (hydrochloride)（2mg/kg/day）处理大鼠28天，增加了大鼠对尼古丁的摄入量[6]。