Distribution of monoamine oxidase proteins in human brain: implications for brain imaging studies

Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [¹¹C]harmine, [¹¹C]clorgyline, and [¹¹C]befloxatone; MAO-B: [¹¹C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution (n=38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [¹¹C]befloxatone (binding potential (BP), r=0.61, P=0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good (P<0.01) for [¹¹C]harmine (distribution volume, r=0.86), [¹¹C]clorgyline (λk₃, r=0.82), and [¹¹C]deprenyl-D2 (λk₃ or modified Patlak slope, r=0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ∼2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality.     

Traditional usage,phytochemistry and pharmacology of the South African medicinal plant Boophone disticha (L.f.) Herb. (Amaryllidaceae)

Ethnopharmacological relevance

Boophone disticha is the most common member of the South African Amaryllidaceae used extensively in traditional medicine of the various indigenous population groups, including the Sotho, Xhosa and Zulu as well as the San. This survey was carried out to identify and highlight areas relevant to the traditional usage of Boophone disticha. Pharmacological aspects were examined with the purpose of reconciling these with the traditional usage of the plant. In relation to phytochemical make-up, particular attention was paid on how its alkaloid constitution might corroborate the various biological effects manifested by the plant.

Materials and methods

Information gathering involved the use of four different database platforms, including Google Scholar, ScienceDirect, SciFinder^® and Scopus. Arrangement and detailing of this information is as reflected in the various sections of the paper.

Results

Sixteen categories were identified under which Boophone disticha finds use in traditional medicine. These were shown to include general usage purposes, such as ‘cultural and dietary’, ‘well-being’, ‘personal injury’, ‘divinatory purposes’, ‘psychoactive properties’ and ‘veterinary uses’. Furthermore, traditional usage was seen to involve six body systems, including functions pertaining to the circulatory, gastrointestinal, muscular, neurological, respiratory and urinary systems. The four remaining categories relate to use for inflammatory conditions, cancer, malaria and tuberculosis. Overall, three areas were discernible in which Boophone disticha finds most usage, which are (i) ailments pertaining to the CNS, (ii) wounds and infections, and (iii) inflammatory conditions. In addition, several aspects pertaining to the toxic properties of the plant are discussed, including genotoxicity, mutagenicity and neurotoxicity.

Conclusion

The widespread ethnic usage of Boophone disticha has justified its standing as a flagship for the Amaryllidaceae and its relevance to South African traditional medicine. Furthermore, its promising pharmacological and phytochemical profiles have stimulated significant interest in the clinical realm, especially in the areas of cancer and motor neuron disease chemotherapy. These collective properties should prove useful in steering the progress of the plant towards a wider audience.     

近5年国内静磁生物效应研究进展*

磁生物效应研究是一门新兴的边缘学科，它以磁场对生物体的影响和作用效果为研究内容，来探讨磁场与生物体之间的关系。近年来随着非药物疗法的兴起，磁场的生物效应受到越来越多的关注。     

丹皮酚对大鼠脑内单胺神经递质的影响

用高效液相色谱－电化学器方法，研究了丹皮酚对大鼠脑内单胺神经递质代谢的影响。结果表明，丹皮酚能增加大鼠纹状体及边缘内多巴胺代谢物高香草酸和三羟苯乙酸含量，也以增加５－羟色胺代谢物５－羟吲哚醋酸的含量，对单胺递质ＮＡ及ＤＡ含量无明显影响。     

In Vitro Evaluation of Bacopa monniera Extract and Individual Constituents on Human Recombinant Monoamine Oxidase Enzymes

Bacopa monniera is a traditional Ayurvedic medicinal plant that has been used worldwide for its nootropic action. Chemically standardized extract of B. monniera is now available as over the counter herbal remedy to enhance memory in children and adults. Considering the nootropic action of B. monniera, we evaluated the effect of clinically available B. monniera extract and six of B. monniera constituents (bacoside A3, bacopaside I, bacopaside II, bacosaponin C, bacosine, and bacoside A mixture) on recombinant human monoamine oxidase (MAO) enzymes. The effect of B. monniera extract and individual constituents on human recombinant MAO‐A and MAO‐B enzymes was evaluated using MAO‐Glo^TM assay kit (Promega Corporation, USA), following the instruction manual. IC₅₀ and mode of inhibition were measured for MAO enzymes. Bacopaside I and bacoside A mixture inhibited the MAO‐A and MAO‐B enzymes. Bacopaside I exhibited mixed mode of inhibition with IC₅₀ and Ki values of 17.08 ± 1.64 and 42.5 ± 3.53 µg/mL, respectively, for MAO‐A enzyme. Bacopaside I is the major constituent of B. monniera, which inhibited the MAO‐A enzyme selectively. Copyright © 2014 John Wiley & Sons, Ltd.     

Monoamine oxidase activity in several structures of rat brain

Spectrophotometric detection (at 327 nm) of a product of the kynuramine oxidation was used to study the distribution of the total activity of monoamine oxidase (MAO) in the hypothalamus, limbic system, dorsal raphe nucleus, locus coeruleus (with surrounding tissues), and hypophysis of female rats. The highest and lowest activities (8.03 ± 0.28 and 0.61 ± 0.05 nmol/min per mg of the protein, M ± m) were found in the median eminence (with its surrounding tissues) and in the hypophysis, respectively. Intermediate values were revealed in the dorsal raphe nucleus (3.10 ± 0.12), medial preoptic area (2.61 ± 0.07), locus coeruleus with its surrounding tissue (2.20 ± 0.22), mammillary body (2.00 ± 0.19), olfactory tubercle cortex (1.43 ± 0.05), and amygdalae(1.41 ± 0.11 nmol/min per mg of the protein). The activity levels of the MAO isoenzymes of types A and B were studied in the median eminence (with its surrounding tissue), dorsal raphe nucleus, medial preoptic area, and the locus coeruleus (with its surrounding tissue). These four structures displayed no significant differences in the activity of MAO A, whereas the MAO B activity decreased in order of the above list of the structures. This indicates that the regional differences in the total MAO activity are determined by the differences in the activity of MAO B.     

单胺氧化酶A基因EcoRⅤ多态与帕金森病的关联分析

目的　研究单胺氧化酶 A(monoamine oxidase A,MAO- A)基因 Eco R 多态 (C/ T)位点在中国人群中的分布 ,并探讨其与帕金森病 (Parkinson's disease ,PD)发病风险的关系。方法　采用聚合酶链反应 -限制性片段长度多态性分析法 ,在 110例 PD患者和 182名正常人中分析了 MAO- A基因 Eco R (C/ T)多态的分布 ,并对该多态与 PD进行关联分析。结果　 (1) MAO- A基因 Eco R 多态与 PD间不存在明显关联 (χ2 =0 .0 91,P=76 .3) ;(2 ) MAO- A基因 Eco R 多态在中国汉族人群和北美高加索人群中的分布差异有显著性 (χ2 =30 .0 3,P=4 .18)。结论　 MAO- A Eco R 多态可能与中国人 PD的发病风险无关     

Brofaromine — a review of its pharmacological properties and therapeutic use

Summary The antidepressant activity of monoamine oxidase inhibitors has been well established for 30 years. Nevertheless, this group of compounds was handled with great care, mainly because of the interaction potential with tyramine-containing foodstuff. With the discovery of reversible and selective inhibitors of monoamine oxidase type A a renaissance of these compounds has begun. In this paper one of these new substances — brofaromine — will be described in detail. Biochemical and pharmacological aspects will be reviewed, showing that brofaromine is a selective and reversible inhibitor of monoamine oxidase type A with additional serotonin reuptake inhibiting properties. Both mechanisms of action may synergize in the antidepressant effect of the compound. The main results of clinical trials in depression and other indication areas will also be covered. Special attention will be put on the side effect profile.Abbreviations A adrenaline - AUC area under curve - BECK Beck Depression Inventory - Bf-S Adjective Mood Scale (von Zerssen) - C _max peak concentration - CGI Clinical Global Impression - DA dopamine - DB double-blind - DSM Diagnostic and Statistical Manual of Mental Disorders - ED effective dose - ECG electrocardiography - EEG electroencephalography - EM extensive metabolizers of debrisoqine - F> _abs absolute bioavailability - GFR glomerulus filtration rate - HAMD Hamilton Depression Scale - 5-HT serotonin - m months - MAO monoamine oxidase - MAOI monoamine oxidase inhibitor - NA noradrenaline - n.a. not applicable - MHPG 3-methoxy-4-hydroxy-phenylglycol - PD presser dose - PEA 2-phenyl-ethyl-amine - PM poor metabolizers of debrisoquine - REM rapid eye movement - _1/2 half-life time - T _max time to peak concentration - VAS visual analogue scale - w weeks - ZUNG Zung Self-Rating Depression Scale     

单胺氧化酶B抑制剂在治疗帕金森病中的研究

理想的帕金森病治疗药物应是既能缓解症状，又能减缓疾病的进展。Safinamide是一种新型单胺氧化酶B（MAO-B）抑制剂，目前正在用于抗痉挛、抗帕金森病和神经保护方面的研究。Safmamide具有独特的分子结构、多重作用机制和很高的治疗指数。它既能高效、选择性和可逆的抑制MAO-B的活性，又能阻断钠、钙通道和抑制谷氨酸的释放。Safinamide还具有极好的的生物利用度、线型动力学、较长的半衰期和良好的安全性及耐受性。本文对主要的MAO-B抑制剂作一介绍。