罂粟碱对大鼠单胺神经递质的影响

本文报道用高效液相色谱-电化学检测器方法,研究了罂粟碱对大鼠脑内及心脏单胺神经递质代谢的影响。结果表明:罂粟碱能显著增加大鼠纹状体及边缘区多巴胺代谢物二羟苯乙酸(DOPAC)和高香草酸(HVA),升高约50-70%。5-羟色胺代谢物5-羟吲哚醋酸(5HIAA)增加约30%,而对脑及心脏内的单胺递质本身含量未见有明显影响。     

囊泡单胺类转运体功能抑制对PC12细胞的毒性及抗氧化剂的干预

目的：研究囊泡单胺类转运体(VMAT)功能抑制对大鼠嗜铬瘤(PC12)细胞产生的内源性毒性及抗氧化剂的保护作用。方法：用流式细胞仪观察VMAT功能抑制以及不同干预方法对PC12细胞存活的影响和细胞死亡方式。结果：单独加入VMAT抑制剂利血平对PC12细胞无毒性作用；利血平协同多巴胺明显增加多巴胺的毒性，使同样浓度的多巴胺诱发PC12细胞的凋亡率明显增加。加入还原型谷胱甘肽(GSH)、二硫苏糖醇(DTF)和脉冲1号使PC12细胞的生存率明显提高。结论：VMAT功能抑制触发了多巴胺内源性毒性可诱发细胞凋亡，具有抗氧化作用的制剂有细胞保护作用。     

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem,caudate/putamen and cortex,and on dopamine D1 and D2 receptors in the caudate/putamen

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D₁ (³[H]SCH 23390) and D₂ (³[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither³[H]SCH 23390 nor³[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.     

Cardiovascular collapse during anesthesia in a patient with preoperatively discontinued chronic MAO inhibitor therapy

We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy was discontinued 20 days before surgery with general anesthesia. This patient developed severe perioperative hypotension after administration of 10 mg of bupivacaine through an epidural catheter, which was corrected only after potent vasopressor therapy. We attribute this hemodynamic instability to attenuation of this patient's sympathetic tone based on several mechanisms: (1) residual effect of long-term administration of MAO inhibitor that caused a decrease in the number of β-adrenergic receptors (adrenergic subsensitivity due to receptor down-regulation), (2) recovered MAO activity causing effective degradation of sympathetic amines, and (3) combined attenuating effects of general and epidural anesthesia on sympathetic tone.     

A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action.

Data now exist from which an accurate definition for serotonin toxicity (ST), or serotonin syndrome, has been developed; this has also lead to precise, validated decision rules for diagnosis. The spectrum concept formulates ST as a continuum of serotonergic effects, mediated by the degree of elevation of intrasynaptic serotonin. This progresses from side effects through to toxicity; the concept emphasizes that it is a form of poisoning, not an idiosyncratic reaction. Observations of the degree of ST precipitated by overdoses of different classes of drugs can elucidate mechanisms and potency of drug actions. There is now sufficient pharmacological data on some drugs to enable a prediction of which ones will be at risk of precipitating ST, either by themselves or in combinations with other drugs. This indicates that some antidepressant drugs, presently thought to have serotonergic effects in animals, do not exhibit such effects in humans. Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose. Tricyclic antidepressants (other than clomipramine and imipramine) do not precipitate serotonin toxicity and might not elevate serotonin or have a dual action, as has been assumed.     

老年大鼠脑内肾上腺素能神经递质系统的变化

本文从下丘脑、大脑皮层、海马等脑区去甲肾上腺素(NA)的含量,其合成酶与降解酶的活性、NA受体数目等多环节的测定来分析肾上腺素能神经递质系统在老化脑中的变化。实验结果表明衰老过程下丘脑、大脑皮层内NA合成酶活性没变化,NA含量明显增高,下丘脑内α_1受体数目显著减少。上述结果提示这些脑区肾上腺素能神经的活动有可能减弱。同时,海马内单胺氧化酶B(MAO B)活性明显增加,说明海马神经元外组织有增生的可能。泰文并讨论了这些变化与老年记忆、行为与神经内分泌等脑功能衰退的关系。     

甲乙型肝炎血清MAO同工酶活性变化研究

用荧光分光光度法检测了血清单胺氧化酶（ＭＡＯ）同工酶Ａ（ＭＡＯ－Ａ）和同工酶Ｂ（ＭＡＯ－Ｂ）活性，结果表明血清ＭＡＯ－Ｂ活性急性期甲肝组较正常对照组显著升高，慢性期乙肝极显著升高；二型肝炎组的ＭＡＯ－Ａ活性升高程度无统计学意义。二型肝炎ＭＡＯ同工酶活性改变与其它肝功生化指标无明显相关性，表现血清ＭＡＯ同工酶活性与肝功损害程度不相关。     

卒中后抑郁患者的认知功能、自主神经功能及血浆单胺类神经递质水平的相关性

目的探讨卒中后抑郁(PSD)患者认知功能、自主神经功能与血浆单胺类神经递质水平的相关性。方法对33例PSD患者(PSD组)和33名健康对照者(正常对照组)进行事件相关电位(ERP)、交感神经皮肤反应(SSR)和血浆单胺类神经递质水平的测定;对检测结果进行Pearson多元相关分析。结果与正常对照组比较,PSD组ERP(P300、N400、CNV及MMN)、SSR各波潜伏期明显延长(均P<0.01),波幅明显下降(均P<0.01);血浆单胺类神经递质水平明显降低(均P<0.01)。PSD组各项指标间均具有相关性(P<0.05～0.01)。结论PSD患者血浆单胺类神经递质水平降低与其认知功能及自主神经功能障碍相关。     

Neurochemical Findings in the Cerebrospinal Fluid of Schizophrenic Patients with Tardive Dyskinesia and Neuroleptic-Induced Parkinsonism

Abstract: Monoamine and their acid metabolites were determined in the CSF of 18 drug-treated chronic schizophrenic patients with the symptoms of tardive dyskinesia and neuroleptic-induced Parkinsonism (Parkinsonism). Six healthy volunteers were used as the control group.
The norepinephrine (NE) levels were found to be significantly higher in the patients with tardive dyskinesia than in the controls. Furthermore, elevated CSF NE levels were also observed in the patients with Parkinsonism. Epinephrine (E) and Dopamine (DA) were not present in the CSF of the control group, whereas measurable levels of DA could be detected in 4 out of 9 and E was found in 8 out of 9 patients with tardive dyskinesia. The mean concentration of HVA was slightly but not significantly elevated in the patients with tardive dyskinesia and Parkinsonism. The mean values of CSF 5-HIAA were all within the normal range in both patient groups. From the above results, it was suggested that abnormal adrenergic activity rather than abnormal dopaminergic activity may play an important role as a mechanism in the etiopathogenesis of extrapyramidal disorders. Furthermore, in the patients with Parkinsonism, CSF neurochemical observations were similar to those of the patients with tardive dyskinesia in this study. It may help to explain the clinical coexistence of tardive dyskinesia and neuroleptic-induced Parkinsonism.     

Is monoamine oxidase inhibitor induced myoclonus serotoninergically mediated?

Summary In the present study a single case observation of myoclonus during sleep-wave transition was monitored in a depressed patient treated with the monoamine oxidase inhibitor, phenelzine. The myoclonus had a rhythm of 1 c/second and lasted for two years, the duration of phenelzine treatment. Myoclonus appeared neither during wakefulness nor during sleep, but at wake-sleep-wake transitions. This switch myoclonus was associated with phasic muscle hyperactivity during REM sleep.Methysergide a 5-HT suppressor, decreased the switch myoclonus frequency and the REM muscle hyperactivity, indicating serotoninergic involvement in the mechanism of phenelzine induced myoclonus.