抗癫痫药物对儿童癫痫病人脑脊液HVA及5-HIAA的影响

用高效液相色谱法,对儿童癫痫病人腰区脑脊液HVA及5-HIAA进行了测定。结果显示:未经药物治疗病人脑脊液5-HIAA 及HVA 与对照组无显著差异;服药患者5-HIAA 则较对照组显著降低。5-羟色胺代谢的改变可能对儿童高级神经活动产生影响。     

钩藤碱对脑缺血大鼠纹状体及海马单胺类递质含量的影响(英文)

目的　探索钩藤碱对大鼠脑缺血损伤的机制。方法　采用大鼠大脑中动脉缺血模型 ,利用微透析方法收集正常及脑缺血后不同时间点纹状体和海马细胞外液 (透析液 )。经反相高效液相电化学法检测其单胺类神经递质含量的变化。结果　大鼠脑缺血后纹状体和海马细胞外液中 5 羟吲哚乙酸 (5 HIAA)、3,4 二羟苯酰乙酸 (DOPAC)和高香草酸(HVA)含量下降 ,去甲肾上腺素 (NE)含量上升 ,钩藤碱能升高脑缺血后细胞外液 5 HIAA ,DOPAC和HVA的含量 ,降低NE的含量。结论　钩藤碱能调节脑缺血大鼠纹状体内和海马单胺类神经递质及代谢物的含量     

精神分裂症病人脑脊液中5－羟色胺及其代谢产物的性别差异

应用高压液相色谱（ＨＰＬＣ）对３０例男性精神分裂症和３７例女性精神分裂症脑脊液（ＣＳＦ）中５─羟色胺（５─ＨＴ）及其代谢产物５─羟吲哚乙酸（５─ＨＩＡＡ）进行测试。结果发现男、女病人ＣＳＦ中５─ＨＴ水平有显著不同，男性病人的５─ＨＴ高于女性病人，而５─ＨＩＡＡ未见显著差异。     

HPLC-ECD法测定大鼠脑组织中单胺类神经递质的含量

目的:建立测定大鼠脑组织中的单胺类神经递质含量的方法。方法:采用高效液相色谱-电化学法,以2,5-二羟基苯甲酸为内标,测定大鼠大脑皮层、小脑、海马组织、下丘脑、嗅球中以去甲肾上腺素(NE)和5-羟色胺(5-HT)为代表的单胺类神经递质的含量。色谱柱为DIKMAC18,流动相为缓冲盐溶液(醋酸钠、庚烷磺酸钠、乙二胺四乙酸二钠和柠檬酸)-甲醇(梯度洗脱),流速为1.0 ml/min,工作电压为+0.7 V。结果:NE、5-HT的检测质量浓度线性范围分别为0.084⁴.2μg/ml(r=0.999 9)和0.0054.2μg/ml(r=0.999 9)和0.005⁰.25μg/ml(r=0.999 1),平均加样回收率分别为98.85%(RSD=2.89%,n=3)和101.5%(RSD=2.41%,n=3),日内(n=5)和日间(n=3)RSD均不大于3%;NE在小脑中的含量最低[(0.343±0.14)mg/g],在下丘脑中含量最高[(3.062±1.51)mg/g];5-HT在小脑中的含量最低[(0.059±0.04)mg/g],在大脑皮层中含量最高[(0.383±0.21)mg/g]。结论:本方法灵敏、简便、快速,可用于大鼠脑组织中NE、5-HT含量的测定。     

利血平和帕吉林对大鼠脑单胺递质含量的联合作用

大鼠ip利血平2mg/kg后1-24h,NE,DA,5-HT均显著下降(p<0.05-p<0.001),5-HIAA则显著升高(p<0.001)。ip帕吉林60mg/kg后1-24h,NE,DA,5-HT均显著升高(p<0.01-p<0.001),5-HIAA则在1-2h内显著下降(p<0.01),4-24h无明显变化。同时使用两药时,对鼠脑NE和DA的影响均呈拮抗作用,对5-HT仅表现帕吉林的作用。帕吉林对利血平化鼠的NE,DA无影响,但可使5-HT升至正常水平;利血平对帕吉林化鼠递质的变化无影响。两药合用对递质的影响表现为拮抗或单一作用,未见递质翻转现象。     

半夏泻心汤对偏头痛大鼠神经递质及早快基因表达的影响

目的 研究半夏泻心汤(BXXXT)对实验性偏头痛模型大鼠神经递质及早快基因表达的影响.方法 将60只SD健康大鼠随机分为正常组、模型组、阳性组、BXXXT高、中、低剂量组.ig生理盐水予正常组、模型组大鼠,其余各组大鼠ig BXXXT,连续7d,末次给药后1h皮下注射硝酸甘油10 mg·kg-1造模.用ELISA法测定大鼠血清中5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)的含量;HE染色观察大鼠脑干组织细胞形态学的变化;免疫组化染色测定大鼠脑干中c-jun基因的表达.结果 与模型组比较,BXXXT可升高大鼠血浆中DA、NE、5-HT的水平,降低5-HIAA水平和大鼠脑干中c-jun基因的表达.结论 BXXXT对实验性偏头痛大鼠具治疗作用.     

中药石菖蒲对脑内单胺类神经递质5-羟色胺水平的影响

目的:观察石菖蒲各提取部分对小鼠大脑内5-羟色胺(5-HT)含量的影响。方法:通过给小鼠灌服石菖蒲不同提取部分,用高效液相色谱-电化学检测法分别测定小鼠大脑内5-HT的含量,研究石菖蒲各提取部分对5-HT含量的影响。结果:小鼠灌服石菖蒲后大脑内5-HT的含量变化如下:石菖蒲挥发油组,石菖蒲水煎液及全方组5-HT的含量均比空白组显著升高(P<0.05,P<0.01,P<0.01)。结论:石菖蒲可显著增加小鼠大脑内5-羟色胺的含量,以此推测石菖蒲很可能通过上调脑内5-HT水平,促进血脑屏障的开放。     

七十味珍珠丸对脑损伤大鼠脑内单胺类神经递质的影响

通过对脑损伤大鼠脑内单胺类神经递质含量的测定,研究七十味珍珠丸治疗脑血管疾病的作用机理.ig给药后,制成脑损伤病理模型,采用荧光分光光度法检测脑内5-羟色胺(5-HT)、去甲肾上腺素(NA)、多巴胺(DA)含量.结果七十味珍珠丸显著降低脑损伤所致大鼠脑内5-HT,NA含量升高,对DA含量的抑制,也有一定作用趋势.     

2,3-吲哚醌对大鼠脑内单胺类神经递质含量与释放的影响

目的研究2,3-吲哚醌对大鼠脑内单胺类神经递质含量与释放的影响。方法给予Wistar大鼠2,3-吲哚醌(50,200 mg.kg-1,ip),2h后测定其纹状体Ach,DA含量;在脑片灌流液中加入2,3-吲哚醌(50,200μmol.L-1),测定其对纹状体及皮质脑片DA,5-HT,NE释放的影响。结果大鼠腹腔给予2,3-吲哚醌,其纹状体Ach和DA的浓度均有增加(P<0.05和P<0.01);脑片灌流液中加入2,3-吲哚醌促进皮质和纹状体内DA释放(P<0.01)。结论2,3-吲哚醌具有调节脑内DA和Ach两种神经递质功能平衡的作用。     

七十味珍珠丸对脑损伤大鼠脑内单胺类神经递质的影响

目的 :通过对脑损伤大鼠脑内单胺类神经递质含量的测定 ,研究七十味珍珠丸 (RNSP)治疗脑血管疾病的作用机理。方法 :RNSP ig给药后 ,制成脑损伤病理模型 ,采用荧光分光光度法检测脑内 5 -羟色胺 (5 -HT)、去甲肾上腺素 (NA)、多巴胺(DA)含量。结果 :RNSP具有显著降低脑损伤所致大鼠脑内 5 -HT、NA含量升高的作用 (P<0 .0 5、P<0 .0 1) ,对 DA含量的抑制 ,也有一定的作用趋势 (P>0 .0 5 )。结论 :RNSP治疗脑血管疾病的作用机理 ,可能与它具有调节脑内单胺类神经递质的作用有关     

CSF monoamine metabolite concentrations vary according to age,rearing, and sex,and are influenced by the stressor of social separation in rhesus monkeys

In humans, CSF monoamine metabolite concentrations have been shown to vary as a complex function of age, sex, psychiatric diagnosis, and stress. To test for such relationships in rhesus monkeys, 28 subjects, reared either in anxiety producing peer-only groups or in mother-infant dyads, were studied at 6, 18 or 50 months of age. Each monkey underwent a series of four 4-day social separations, each followed by 3 days of reunion. Prior to and during the first and fourth separations, CSF was obtained from the cisterna magna and assayed for the serotonin metabolite 5-HIAA, the dopamine metabolite HVA, and the norepinephrine metabolite MHPG. CSF 5-HIAA showed an age-related decline which was greater in the mother-reared subjects. Peer-only-reared males had an increased 5-HIAA concentration relative to females, and higher 5-HIAA levels than mother-reared males. MHPG was also higher in peer-only-reared monkeys than in mother-reared subjects at all ages. In both groups HVA declined across the three ages, and MHPG increased from the 18- to the 50-month measurements. Both MHPG and 5-HIAA concentrations increased during the initial social separation, although only MHPG remained elevated across the repeated separations; HVA, on the other hand declined during social separation. These results are discussed in terms of established anxiety and aggression differences between peer-only and mother-reared monkeys.     

Dystrobrevin-binding protein 1 gene (DTNBP1) variants associated with cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in healthy volunteers

The dystrobrevin binding protein-1 (DTNBP1) gene encodes dysbindin-1, a protein involved in neurodevelopmental and neurochemical processes related mainly to the monoamine dopamine. We investigated possible associations between eleven DTNBP1 polymorphisms and cerebrospinal fluid (CSF) concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy human subjects (n = 132). Two polymorphisms, rs2619538 and rs760666, were nominally associated with CSF HVA and 5-HIAA concentrations, whereas a third polymorphism, rs909706, showed association only with HVA. After correction for multiple testing only the associations between rs2619538 and HVA and 5-HIAA concentrations remained significant. No significant association was found between any of the investigated DTNBP1 polymorphisms and CSF MHPG concentrations. The results suggest that genetic variation in DTNBP1 gene affects the regulation of dopamine and serotonin turnover in the central nervous system of healthy volunteers.     

Determinations of 5-hydroxyindoleacetic acid and homovanillic acid in human CSF with monitoring of probenecid levels in CSF and plasma

The accumulation of 5-HIAA and HVA in cerebrospinal fluid (CSF) was studied in eight healthy volunteers after oral administration of probenecid. Simulation indicated that a dose of 4.5 g probenecid should be used to achieve probenecid plasma concentrations between 200 and 400 g/ml. Almost complete inhibition of the active transport of the acidic metabolites was assumed to be obtained at these concentrations. Probenecid 4.5 g was administered in two doses (2.5 g and 2 g), separated by 4 h. Plasma samples were drawn at varying intervals over a period of 46 h and lumbar puncture (LP) was performed at either 14 h or 20 h after the first administration of probenecid. The concentration of probenecid, 5-HIAA and HVA in CSF was estimated and the probenecid-induced accumulation of 5-HIAA and HVA was compared with their baseline values. There were no statistically significant differences (P>0.05) in the accumulation of the monoamine metabolites between the two LP (14 h and 20 h), neither were there any differences in CSF concentrations of probenecid at the time of LP. There were only small differences in probenecid plasma concentrations, although statistically significant. Due to maximum blockade of the active transport system no correlation was observed between the CSF concentration of probenecid and the induced accumulation of 5-HIAA and HVA, respectively. The range of probenecid-induced accumulation for 5-HIAA and HVA in these volunteers was 156–429% and 183–600%, respectively. The suggested monitoring of probenecid plasma levels is proposed as a suitable model to investigate central neuronal activity of dopamine and serotonin in the central nervous system.     

Effects of acute and chronic phenelzine on regional monoamine metabolism in rats and its potentiation by deuterium substitution

Summary Phenelzine is a monoamine oxidase inhibitor with antidepressant properties. The present study investigated effects of acute (1–2 mg kg^–1 4h s.c.) and chronic (0.25–2 mg kg^–1 day^–1 Alzet miniosmotic pumps, 13 days s.c.) administration of phenelzine on regional monoamine metabolism in rats. The effects of these phenelzine treatments were compared with those of equivalent doses of a deuterated form of the drug (phenelzine-d₄). The following brain regions and compounds were assessed using high performance lipuid chromatography with electrochemical detection: Striatum: dopamine, DOPAC, HVA, 5-HT, 5-HIAA; hypothalamus: dopamine, 5-HT, 5-HIAA, noradrenaline; hippocampus: 5-HT, 5-HIAA, noradrenaline; frontal cortex: dopamine, noradrenaline, 5-HT, 5-HIAA. Acute drug administration increased levels of dopamine, 5-HT and noradrenaline with the exception of dopamine in the hypothalamus and frontal cortex and 5-HT in the hypothalamus. DOPAC, HVA and 5-HIAA levels were decreased. After chronic administration amine levels increased with the exception of dopamine administration amine levels increased with the exception of dopamine in the hypothalamus. The respective acid metabolites were also decreased. These effects of phenelzine were markedly potentiated by deuterium which was substituted for hydrogen in the side chain. The potentiation of these effects was enhanced with chronic administration, differences between phenelzine and phenelzine-d₄ effects being more marked at lower doses.     

The effect of propranolol treatment in schizophrenia on CSF amine metabolites and prolactin

Recent reports have suggested that high doses of propranolol may be an effective treatment in schizophrenia. To determine whether such treatment has effects on cerebrospinal fluid (CSF) amine metabolites and prolactin similar to the effects of the neuroleptic drugs, we studied CSF from ten patients before and after propranolol therapy. The initial CSF sample was removed after a drug-free period and propranolol dosage was then increased over 1 week to 1000 mg daily in all ten patients. A second CSF sample was removed after 3 weeks of propranolol therapy. Propranolol levels and prolactin in CSF were measured by radioimmunoassay. Homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were measured by gas chromatography-mass spectrometry. Propranolol had no effect on the prolactin or amine metabolite concentrations. CSF propranolol levels averaged 40 ng/ml (range <1–78).     

Effect of theophylline on monoamine metabolism in the rat brain

The effect of theophylline on brain monoamine metabolism was studied in rats. Single doses of theophylline caused a striking and dose-related increase in the levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MOPEG-SO₄) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. The level of brain homovanillic acid was only slightly affected. No appreciable change occurred, however, in the levels of brain norepinephrine, serotonin and dopamine. The increased level of brain MOPEG-SO₄ or 5-HIAA after theophylline does not appear to result from its interference with the transport system for the acids in the brain since the rate of decline of the acid levels following pargyline was not affected. Under the conditions of brain monoamine oxidase inhibition, theophylline enhanced the increase in brain normetanephrine level without causing any change in 3-methoxytyramine level. The enhancement of brain normetanephrine level by theophylline became more pronounced when rats were pretreated with imipramine in addition to pargyline.These results suggest that, in the brain, theophylline may cause a release of serotonin leading to its increased turnover. The results also confirm the previous conclusion that the methylxanthine causes a release of norepinephrine and a concomitant increase in its turnover in the brain.     

Effects of tiapride on homovanillic acid levels in human cerebrospinal fluid drawn at pneumoencephalography

The effect of tiapride on HVA and 5-HIAA levels in the CSF drawn at pneumoencephalography (PEG) was studied. Five consecutive 5 ml fractions of CSF were drawn from control and tiapride-treated subjects. In both groups, a linear increase in HVA concentrations was found between the first and subsequent fractions. On the contrary, no significant difference in 5-HIAA concentrations was found in sequential CSF samples. Tiapride increased the mean HVA concentrations and caused a steeper caudocranial gradient of this metabolite but failed to modify 5-HIAA concentrations. The results suggest that tiapride blocks dopamine (DA) receptors and increases DA synthesis.     

An open study of risperidone liquid in the acute phase of schizophrenia

An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity.     

The dynamics of dopamine metabolism in various regions of rat brain

Dopamine metabolism was studied in various regions of rat brain by following the decline of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) from brain after treatment with pargyline, or from the accumulation of the acids after treatment with probenecid. The decline of DOPAC and HVA after pargyline treatment appeared exponential in all regions of brain studied with half-lives of about 13 min for HVA and 6.5 min for DOPAC. DOPAC was the major metabolite of dopamine, with various brain regions producing between 2–5 times more DOPAC than HVA. HVA accumulated after treatment with probenecid but the accumulation in 1 h did not account for all of the HVA apparently eliminated from brain. DOPAC accumulated in some regions of brain (medulla, hypothalamus and midbrain) and not in others (cerebellum, cortex, striatum and hippocampus) after probenecid treatment. We conclude that dopamine metabolism is not uniform in brain and that the accumulation of DOPAC and HVA in brain after probenecid treatment only accounts for a minor fraction of the dopamine formed in brain.