千金藤啶碱对大鼠脑内单胺代谢的影响

1-千金藤啶碱(1-SPD 15～120 mg/kg)能增加大鼠纹状体和边缘区的多巴胺代谢物DOPAC和HVA(+150～300%),并有剂量相关关系。此作用于给药后60 min达峰值,给药后4 h虽有恢复趋势,但仍明显高于对照值。SPD还能中等度地降低上述两个脑区的DA和NA(-18～48%)。DA转换率(表现为代谢物增加)的升高支持SPD为DA受体阻断剂。但DA和NA下降表明,除有受体阻断作用外,不能排除药物对单胺递质的贮存、释放或再摄取的影响。纹状体内的5-HIAA含量亦有明显升高。     

千金藤啶碱对大鼠脑内单胺代谢的影响

1-千金藤啶碱(1-SPD 15～120 mg/kg)能增加大鼠纹状体和边缘区的多巴胺代谢物DOPAC和HVA(+150～300%),并有剂量相关关系。此作用于给药后60 min达峰值,给药后4 h虽有恢复趋势,但仍明显高于对照值。SPD还能中等度地降低上述两个脑区的DA和NA(-18～48%)。DA转换率(表现为代谢物增加)的升高支持SPD为DA受体阻断剂。但DA和NA下降表明,除有受体阻断作用外,不能排除药物对单胺递质的贮存、释放或再摄取的影响。纹状体内的5-HIAA含量亦有明显升高。     

次黄嘌呤对单胺氧化酶的抑制作用

实验证明给小鼠po次黄嘌呤25～500 mg/kg时,对肝和脑中单胺氧化酶B(MAOB)活性的抑制作用与剂量成明显的量—效关系,对MAO-A活性的抑制较弱,且无明显的量—效关系。给小鼠一次po次黄嘌呤500 mg/kg,于给药后16h,对MAO抑制作用最明显。sc时,对肝中MAO活性抑制也以给药后16 h最明显,但对脑中MAO活性抑制不明显。离体实验证明,次黄嘌呤对MAO-B的抑制为竞争性,对MAO-A则为混合型抑制。     

ANTICONVULSANT ACTIVITY OF DI-N-PROPYLACETATE AND BRAIN MONOAMINE METABOLISM IN THE RAT

1. Sodium di-n-propylacetate (DPA) treatment induced significant increases in brain contents of gamma-aminobutyric acid (GABA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). Furthermore, the threshold for pentylenetetrazol (PTZ) clonic convulsions was also increased in response to DPA administration. 2. Pretreatment with inhibitors of monoamine synthesis alpha-methyl-p-tyrosine (AMPT) and p-chlorophenylalanine (PCPA) did not alter the anticonvulsant activity of DPA, but when given alone, both AMPT and PCPA caused significant decreases in brain monoamine contents and PTZ threshold seizures. 3. Experiments using probenecid suggest that the increases in 5-HIAA and HVA seen after DPA treatment could have resulted from inhibition of their active transport out of the brain. These data indicate that the anticonvulsant action of DPA is not dependent on changes in monoamine metabolism in the brain.     

吡喹酮对大鼠单胺介质的影响

吡喹酮是一种新型广谱抗寄生虫药。本文报道用高效液相色谱-电化学检测器联用的方法,测定单胺类神经介质及其代谢物的含量,研究吡喹酮对大鼠单胺类介质的影响。结果表明:吡喹酮(250 mg/kg使脑DA的酸性代谢产物DOPAC,HVA和5-HT的代谢物5-HIAA的含量明显升高,而对DA和NA含量无明显影响。DA酸性代谢物和5-HIAA升高表明吡喹酮能增加DA和5-HT的转换率。     

吡喹酮对大鼠单胺介质的影响

吡喹酮是一种新型广谱抗寄生虫药。本文报道用高效液相色谱-电化学检测器联用的方法,测定单胺类神经介质及其代谢物的含量,研究吡喹酮对大鼠单胺类介质的影响。结果表明:吡喹酮(250 mg/kg使脑DA的酸性代谢产物DOPAC,HVA和5-HT的代谢物5-HIAA的含量明显升高,而对DA和NA含量无明显影响。DA酸性代谢物和5-HIAA升高表明吡喹酮能增加DA和5-HT的转换率     

THE INFLUENCE OF BENSERAZIDE ON CHANGES IN MONOAMINE OXIDASE ACTIVITY IN SOME RAT TISSUES FOLLOWING TREATMENT WITH L-DOPA

• 1 This study was designed to see whether or not increases in monoamine oxidase (MAO) specific activity that follow chronic treatment of rats with L-dihydroxyphenylalanine (L-DOPA) could be modified by benserazide (Ro 4-4602), an inhibitor of L-aromatic amino acid decarboxylase, and to compare the properties of the increased MAO activity with those of control animals.
• 2 Male Wistar rats were treated with L-DOPA (250 mg/kg) and benserazide (40 mg/kg) either alone or in combination for 10 days.
• 3 The activity of MAO in homogenates of heart, kidney, liver and brain was measured with 5-hydroxytryptamine (5-HT) and benzylamine (BZ).
• 4 The significant increases in MAO specific activity seen in heart and kidney following L-DOPA treatment could be reduced or prevented by benserazide.
• 5 Use of the selective MAO inhibitor clorgyline showed that the increases in MAO specific activity, when measured with either 5-HT or BZ were due to an increase in the number of active centres of MAO-A, in the rat heart.
• 6 There was a significant increase in the V max of the enzyme reaction with 5-HT, in the rat heart and kidney homogenates.
• 7 It is concluded that L-DOPA increases the specific activity of MAO-A in rat heart and kidney as a result of its decarboxylation.

     

小柴胡汤对大鼠肝线粒体的单胺氧化酶的抑制作用

小柴胡汤对大鼠肝线粒体单胺氧化酶B(MAO-B)有显著的抑制作用。IC~(50)为91.20mg/ml.单味药研究表明,组成小柴胡汤的7味中药显著地抑制MAO-B活性。按作用强弱依次为甘草>半夏>柴胡>党参>大枣>生姜>黄芩。动力学研究表明,小柴胡汤对MAO-B活性抑制作用属底物竞争性抑制。提示小柴胡汤对肝脏疾患及神经功能失调的治疗作用可能与其对MAO的抑制有关。     

PLATELET MONOAMINE OXIDASE ACTIVITY IN PATIENTS WITH HUNTINGTON''S DISEASE

1. Platelet monoamine oxidase (MAO) activity was investigated in 30 patients with Huntington's disease and compared with the activity in a control group. 2. Significantly elevated activity was found in the patients (P less than 0.05; t-test) when same sex contrasts were carried out to account for the well known influence of sex on MAO activity. 3. The mean MAO activity in male patients was 23.5 +/- 6.0 nmol/mg protein per h and female patients was 29.5 +/- 8.9 nmol/mg protein per h using tyramine as the substrate. 4. The possible influence of environmental factors on the results is discussed.     

某些异喹啉类生物碱对大鼠脑内单胺的影响

1-四氢巴马汀(1-THP)和四氢小檗碱(THB)与dl-THP一样都能降低脑内单胺和升高酸性代谢产物DOPAC,HVA和5-HIAA。它们作用的强弱次序为dl-THP<1-THP相似文献   

某些异喹啉类生物碱对大鼠脑内单胺的影响

1-四氢巴马汀(1-THP)和四氢小檗碱(THB)与dl-THP一样都能降低脑内单胺和升高酸性代谢产物DOPAC,HVA和5-HIAA。它们作用的强弱次序为dl-THP<1-THP相似文献   

四氢异喹啉类生物碱对大鼠脑内α肾上腺素受体的作用

应用放射受体结合法研究了近30种四氢异喹啉类(TIQs)生物碱对大鼠脑内α肾上腺素受体的作用。其中l-CBN,l-THC和l-STP对α₁受体亲和力最高,K_i值为～2.0×10^-7mol/L。其次是DHS,XLP和l-DCT,K_i值分别为4.7×10^-7,6.5×10^-7和7.6×10^-7mol/L。DHS对α₂受体亲和力最高(K_i=1.25×10^-6mol/L),l-REM次之。对α受体亚型亲和力选择比K_i(alpha-2)/Ki(alpha-1)最高的是l-STP(357) 和XLP(154),它们对α₂受体几无亲和力(K_i>10^-4mnl/L)。提示l-STP和XLP对α₁受体有较高的选择性。l-SPD和l-THP对α₁和α₂受体亲和力相近,均为中等强度。THJ,DRC及l-TTD等6种TIQs对α₁和α₂受体均无亲和力(K_i>10^-4mnl/L)。     

人参茎叶皂甙及其单体对大鼠脑内B型单胺氧化酶活性的影响

本文用体外法研究了人参茎叶皂甙(GSLS)及其单体Rg_1,Rg_2,Re和Rh_1大鼠脑内B型单胺氧化酶(MAO-B)活性的影响。结果表明,GSLS和Rh_1可加强MAO-B的活性。Rg_1和Rg_2可抑制MAO-B的活性,其抑制强度与3.3×10~(-5)mg/ml优降宁相当。抑制特征曲线表明Rg_1和Rg_2对MAO-B的抑制作用均属竞争性抑制。     

ACUTE EFFECTS OF A BICYCLOPHOSPHATE NEUROCONVULSANT ON MONOAMINE NEUROTRANSMITTER AND METABOLITE LEVELS IN THE RAT BRAIN

Naive male Sprague-Dawley rats were injected intraperitoneally (ip) with the bicyclophosphate convulsant trimethylolpropane phosphate (TMPP) at dose levels from 0.2 to 0.6 mg/kg. Rats were observed for convulsive activity, and were sacrificed 15 min posttreatment. Levels of the monoamine neurotransmitters norepinephrine (NE), epinephrine (EPI), dopamine (DA) , and serotonin (5-HT) and the major metabolites 3,4- dihydroxyphenylacetic acid ( DOPAC) , homovanillic acid ( HVA) , and 5-hydroxyindoleacetic acid ( 5-HIAA) were assayed in forebrain, midbrain, hindbrain, cerebellum and brainstem regions. Neurotransmitter and metabolite levels were compared between control rats and rats that did and did not experience seizures. TMPP administration induced significant decreases in levels of measured neurotransmitters that varied as a function of brain region, dose, and expression of the seizure activity. These results show that tonic or tonic-clonic seizures induced by TMPP administration (0.6 mg/ kg) are reliably associated with regional decreases in serotonin, dopamine, and norepinephrine. Convulsive activity resulting from lower dose administrations (0.2-0.4 mg/kg) of TMPP result only in decreased regional levels of serotonin.     

LACK OF EFFECT OF CHLORAMPHENICOL ON MONOAMINE, DIAMINE AND PLASMA AMINE OXIDASE ACTIVITIES

Chloramphenicol treatment in rabbits (60 mg/kg i.m. for 5 days) did not affect significantly (P greater than 0.1) the activities of monoamine oxidase (MAO) or diamine oxidase (DAO) in liver, heart or brain. Plasma amine oxidase (PAO) was not significantly inhibited (P greater than 0.1) in goats treated with chloramphenicol (60 mg/kg i.m. for 5 days). Chloramphenicol (2 X 10(-3) mol/l) preincubated with rabbit hepatic MAO had no significant effect (P greater than 0.1) on the enzyme activity.     

EFFECT OF CAPTOPRIL ON BRAIN CONVERTING ENZYME IN THE SPONTANEOUSLY HYPERTENSIVE RAT

The effect of oral captopril (30 mg/kg per day) on the blood pressure, plasma aldosterone concentration, urinary electrolytes and brain angiotensin-converting enzyme activity of spontaneously hypertensive rats of the Okamoto strain was examined. Over a seven day period, captopril caused a progressive fall in blood pressure with increased sodium excretion and urine volume and a significant fall in plasma aldosterone concentration. Following captopril, angiotensin converting enzyme activity increased significantly in the midbrain and medulla oblongata; the pituitary level of angiotensin converting enzyme activity was significantly decreased. The hypotensive action of captopril in the spontaneously hypertensive rat is associated with changes in body sodium, water and plasma aldosterone concentration. The alterations in brain angiotensin-converting enzyme activity following captopril treatment suggest that, with chronic administration, captopril can alter the activity of the brain renin-angiotensin system.     

四氢巴马汀对大鼠伏核单位放电的影响

用清醒制动大鼠记录了前脑伏核神经元的自发放电。伏核单位放电率为4.9次/s。四氢巴马汀(THP)明显抑制伏核单位放电。抑制效应在给药后10 min开始,30 min时最明显。单胺氧化酶抑制剂优降宁对伏核放电无明显影响,但能消除THP对伏核放电的抑制作用。本研究结果和THP排空单胺介质的生化资料结果一致,可以认为THP为利血平样作用的单胺排空剂。     

HEMODYNAMICS AND MONOAMINE OXIDASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS (SHR)

The relationship between the onset of hypertension and changes in monoamine oxidase (MAO) activity in the brains and hearts of spontaneously hypertensive rats (SHR) were studied. After 7-weeks-old, blood pressure of SHR increased rapidly and reached a level of 170 to 180 mmHg; but following 4 weeks of propranolol treatment (10 mg/kg/day), blood pressure decreased significantly compared to that of untreated SHR. Heart/body weights ratio of SHR was higher than that of normotensive Wistar Kyoto rats (WKY). MAO activities in the brain stem, the medulla oblongata and pons of the SHR were significantly higher than those in WKY at 7 weeks of age, and MAO activity in the brain stem of the propranolol-treated SHR was significantly lower than that in the untreated SHR. Propranolol inhibited MAO activity in brain tissue in vitro, and the l₅₀ values of propranolol were identical (1 × 10^-4 M) in SHR and WKY. In both the WKY strain and the SHR, the V_max values of heart MAO increased with age, and the V_max values of SHR were twice those of WKY. K_m values for tyramine of heart MAO in WKY and SHR were approx. 100 μM and 140 μM. respectively; however, these values were not age-dependent. It was concluded that an increase in MAO activity in SHR brain stem may trigger a reduction in noradrenaline content and that propranolol may be responsible for its restoration, thus reducing peripheral sympathetic activity; moreover, the increase in MAO activity in the hearts of SHR may be of genetic origin.