用混合植物组织碳糊生物微电极在体测定大鼠纹状体内多巴胺含量

应用混合植物组织碳糊生物微电极在体测定了活大鼠纹状体内多巴胺(DA)含量。该电极灵敏度和选择性良好,检出下限为32.5 n mol/L。抗坏血酸(AA)、肾上腺素(E)、5-羟色胺酸(5-HTP)在此电极上有良好的阳极峰,而且与DA峰完全分离,不干扰DA的测定。5-羟色胺(5-HT)对DA的测定也无明显影响。应用该生物微电极在体动态地观察了给予左旋多巴(L-DOPA)及利血平后活体大鼠纹状体内DA含量的变化,电极稳定性好,在体内可以连续工作10h左右。     

孕酮对大鼠吗啡奖赏效应及下丘脑和纹状体内单胺递质水平的影响

目的:观察孕酮对于吗啡所致奖赏效应及下丘脑、纹状体内单胺类神经递质水平的影响。方法:采用大鼠条件性位置偏爱(CPP)模型,建立离体电化学检测技术高效液相色谱法测定大鼠下丘脑及纹状体内去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的含量。结果:吗啡(5mg·kg-1)可诱导大鼠产生稳定的CPP效应;孕酮(5mg·kg-1及20mg·kg-1)本身不产生CPP效应,但能抑制吗啡诱导的CPP效应。与对照组比较,吗啡诱导CPP形成时,下丘脑内NE水平明显升高(P<0.05),纹状体内NE、DA和HT的水平明显升高(P<0.05,P<0.01)。与吗啡组比较,合用20mg·kg-1孕酮使纹状体内DA水平显著下降(P<0.01)。结论:孕酮对吗啡的CPP效应具有一定的抑制作用,其机制可能与降低纹状体内DA水平有关。     

伏安法测定MK-801和五味子醇甲对DA/DOPAC的影响

用差示复位脉冲伏安法(DNPV)在体测定了大鼠纹状体细胞外液中DA/DOPAC含量在缺血和再灌期的动态变化,并观察了MK-801和五味子醇甲对DA/DOPAC变化的影响,结果表明缺血6分钟期间DA/DOPAC峰显著增高,再灌流后,峰高逐渐下降,(+)MK-801和五味子醇甲均能显著抑制缺血后纹状体内DA的释放。     

微透析取样和微柱液相色谱电化学检测法测定大鼠脑纹状体中的5-羟色胺

目的:建立一个测定生物样本中5-羟色胺的灵敏方法.方法:将微透析取样和微柱液相色谱电化学检测(LCEC)有机结合,建立灵敏的分析方法.结果:很容易地测定了自由活动大鼠脑纹状体透析液中fg-pg的5-羟色胺变化.结论:本法对生物活体研究很有用.健康大鼠脑纹状体内5-羟色胺水平是相当稳定的.     

用在体脑微透析技术研究大鼠纹状体中单胺递质的释放和代谢

采用脑微透析技术与高效液相色谱-电化学检测器联用测定了清醒自由活动大鼠纹状体细胞外液中多巴胺(DA)及其酸性代谢物3,4-二羟苯乙酸(DOPAC)和高香草酸(HVA)以及5-羟色胺代谢物5-羟吲哚乙酸(5-HIAA)的含量.透析液中DA为0.44 pmol/40μl,DOPAC和HVA含量较DA高约80倍.右旋苯丙胺2 mg/kg,ip使纹状体DA释放显著增加,DOPAC和HVA含量明显下降.     

伏安法测定MK—801和五味子醇甲对DN／DOPAC的影响

用差示复位脉冲伏安法（DNPV）在体测定了大鼠纹状体细胞外液中DA／DOPAC含量在缺血和再灌期的动态变化，并观察了MK－801和五味子醇甲对DA／DOPAC变化的影响，结果表明缺血6分钟期间DA／DOPAC峰显著增高，再灌流后，峰高逐渐下降。（＋）MK－801和五味子醇甲均能显著抑制缺血后纹状体内DA的释放。     

吗啡依赖大鼠纹状体内神经甾体水平的变化

目的:探讨吗啡躯体依赖、精神依赖和戒断对♂大鼠纹状体内神经甾体水平的影响。方法:高效液相色谱-质谱法测定大鼠纹状体和血浆中脱氢表雄酮(DHEA)及其硫酸酯(DHEAS)、孕烯醇酮(PREG)及其硫酸酯(PREGS)和别孕烯醇酮(AP)的含量。结果:(1)与纳洛酮对照组比较,纳洛酮催促吗啡戒断大鼠的纹状体内PREG的含量显著升高(P<0.01);血浆中PREG、AP、DHEAS和PREGS的含量显著升高(P<0.01),而DHEA的含量显著降低(P<0.01);(2)与生理盐水对照组比较,吗啡精神依赖大鼠的纹状体内DHEA和PREG的含量显著升高(P<0.01),血浆中DHEA的水平显著降低(P<0.01)。结论:慢性吗啡处理可影响大鼠纹状体内某些神经甾体的水平,表明神经甾体可能参与吗啡依赖的形成。     

都可喜对慢性间断性缺氧大鼠学习记忆能力及脑内单胺类神经递质的影响

目的:探讨都可喜(Duxil,阿米三嗪+萝巴新)对慢性间断性缺氧(EHYP)大鼠学习记忆能力和脑内单胺类神经递质水平的影响。方法:建立EHYP大鼠模型,并给予Duxil(0.03片·350g~(-1)体重,bid)干预。用被动避暗回避反射试验评价大鼠学习记忆能力,潜伏期(STL)越长,学习记忆能力越强;用高效液相色谱电化学检测器法测定大鼠皮层、海马和纹状体内去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)等单胺类神经递质的含量。结果:与对照组相比,EHYP组大鼠STL明显缩短(P<0.01),各脑区单胺类神经递质水平显著降低(P<0.05)。与EHYP组相比,Duxil组大鼠STL显著延长(P<0.01),皮层NE和DA含量、海马NE,DA和5-HT含量以及纹状体NE,DA和5-HT含量显著升高(P<0.05)。结论:Duxil可改善EHYP大鼠学习记忆能力并提高脑内单胺类神经递质水平。     

多巴胺在聚变色酸2B膜电极上的电化学行为及其测定

目的:研究多巴胺(DA)在聚变色酸2B 膜(PCR2B)修饰电极上的伏安行为,建立测定 DA 含量的差示脉冲伏安法。方法:采用循环伏安法研究 DA 在膜修饰电极上的电化学行为,以差示脉冲伏安(DPV)对其含量进行测定。结果:聚变色酸2B 膜修饰电极对 DA 有明显的电催化作用。在 pH 5.0磷酸盐缓冲液(PBS)中,氧化峰电流与 DA 浓度在2.0×10~(-6)～1.0×10~(-5)mol·L~(-1)范围内呈良好的线性关系,检测限为3.2×10~(-7)mol·L~(-1)。结论:该修饰电极可有效消除针剂中其他组分对 DA测定的干扰,可用于实际样品中 DA 含量的直接测定。     

活化玻碳电极直接测定注射液多巴胺的含量

目的:研究多巴胺(DA)在活化玻碳电极(AGCE)上的电化学行为,建立一种测定多巴胺(DA)的电化学分析方法。方法:玻碳电极在0.1 mol·L~(-1)磷酸盐缓冲液(pH 7.0)中活化,用循环伏安法研究 DA 在活化玻碳电极上的氧化还原特性,用微分脉冲伏安法直接测定 DA 的含量。结果:DA 在活化玻碳电极上的循环伏安图具有一对灵敏的氧化还原峰,峰电位分别为0.167 V 和0.217 V(vs.SCE)。与裸玻碳电极相比,该电极对 DA 的氧化具有良好的电催化作用。微分脉冲伏安法测定 DA 的氧化峰电流与其浓度在2个区间成正比,分别为1.0×10~(-6)～2.5×10~(-5)～mol·L~(-1)和2.5×10~(-5)～2.5×10~(-4)mol·L~(-1),线性相关系数分别为0.9931和0.9938,检出限5.0×10~(-7)～mol·L~(-1)。抗坏血酸(AA)和尿酸(UA)对 DA 的测定均没有干扰。结论:该方法操作简单方便,重现性较好,用于测定多巴胺注射液中 DA 的含量,结果令人满意。     

Formulation and evaluation of in situ gelling system of dimenhydrinate for nasal administration

Nasal drug delivery has a variety of advantages. Drugs can be rapidly absorbed through the nasal mucosa, giving rapid onset of action, and avoiding presystemic metabolism. In present study; the nasal mucoadhesive in situ gels of anti-emetic drug Dimenhydrinate were formulated using Gellan gum and Carbopol 934P. The in situ gels so prepared were characterized for gelation, viscosity, gel strength, mucoadhesion, drug content, drug diffusion, ex vivo permeation and histopathological studies. The optimized formulation passing from above tests was further subjected to accelerated stability study. It retained the good stability over the period of 90 days. From the overall performance this in situ gel seems to be an effective delivery system for the nasal route.     

人工脑脊液样本中多巴胺的稳定性研究

目的:建立测定多巴胺在人工脑脊液中含量的测定方法,考察多巴胺在加入稳定剂后人工脑脊液中的稳定性。方法:采用HPLC-电化学检测法,考察多巴胺在加入稳定剂后于冷藏、冷冻及反复冻融不同条件下的稳定性。结果:多巴胺的保留时间为6.2min,线性范围是0.05⁵nmol·L5nmol·L^(-1),日内与日间精密度均<5%,回收率在99.9%(-1),日内与日间精密度均<5%,回收率在99.9%¹01.6%之间。加入稳定剂后,多巴胺人工脑脊液溶液稳定性显著提高,4℃冰箱内至少能稳定放置3d,在-70℃冰冻条件下至少能稳定放置1周,样品反复冻融3次稳定。大鼠给予氟哌啶醇后,前额叶皮层中多巴胺含量基本无影响,伏隔核中多巴胺显著升高。结论:加入稳定剂后,多巴胺的稳定性显著提高,适用于脑微透析样品中多巴胺的定量分析。     

Neuroleptic blockade of the effect of various neurotransmitter substances.

The antagonistic effect of neuroleptics to acetylcholine, histamine, 5-HT, and noradrenaline was examined in various in vivo and in vitro models. Piflutixol, a new potent thioxanthene neuroleptic, markedly antagonizes the effect of dopamine, noradrenaline, 5-HT and to some extent histamine, whereas the affinity for muscarinic receptors was rather weak. Clozapine and chlorprothixene on the other hand, have high affinity for muscarinic receptors and also antagonize the effect of histamine and 5-HT, whereas clozapine was a weak antagonist of noradrenaline and dopamine when compared to the effect of piflutixol. Chlorprothixene, however, also exhibits a rather good antagonism of noradrenaline and dopamine. Haloperidol proved to be weak in all models when compared with the other neuroleptics examined. Flupenthixol specifically antagonizes dopamine and noradrenaline, whereas fluphenazine was a more potent antagonist of dopamine than of the other transmitters. The data show, that neuroleptic compounds possess very different profiles with regard to interaction with various neurotransmitter substances. It is suggested, that the rather potent anti 5-HT and antihistamine effects observed for certain substances may contribute to the central effect of these drugs.     

Stability of dopamine hydrochloride exposed to blue-light phototherapy

The stability of dopamine hydrochloride in 5% dextrose injection when exposed to blue-light phototherapy was assessed. Solutions of dopamine hydrochloride (1000 micrograms/mL) were prepared, and samples were subjected to one of three light sources (fluorescent, dark, phototherapy) and two flow rates (2 mL/hr and no flow) at ambient room temperature. Irradiation levels were maintained between 5.1 and 6.6 microwatts/sq cm throughout the experiment. Samples obtained at 0 to 36 hours were assayed using high-performance liquid chromatography. There were no significant differences in dopamine stability among the sample groups exposed to the various light and flow conditions over the 36-hour study period. Dopamine hydrochloride in 5% dextrose injection exposed to phototherapy is stable for 36 hours at 1000 micrograms/mL. It is not necessary to protect dopamine solutions from blue-light irradiance to ensure clinically acceptable stability.     

Interaction of the component enantiomers of the putative dopamine autoreceptor agonist,TL-99 (6,7-dihydroxy-2-dimethylamino tetralin) with dopaminergic systems in mammalian brain and teleost retina

The enantiomers of the putative dopamine autoreceptor agonist, TL-99 (6,7-dihydroxy-2-dimethylaminotetralin) were examined in a number of in vivo and in vitro test paradigms to further examine the reported autoreceptor selectivity of this compound. The (+)-isomer of the aminotetralin was more active as a dopamine agonist than either the racemate or the (-)-enantiomer. In addition to this dopaminergic activity, TL-99 was found to be a potent alpha 2-adrenoceptor agonist, this activity being more prominent in the (+)-isomer. The (-)-isomer, however, was a weak alpha 2/DA receptor agonist and unlike the (+)-enantiomer was devoid of activity in the D-1-selective carp retina adenylate cyclase assay. Pharmacological examination of the effects of TL-99 on mouse locomotor activity showed that the effects of the aminotetralin in this dopamine autoreceptor test system were antagonized by either the alpha 2-antagonist, yohimbine or by the dopamine antagonist, sulpiride. TL-99 also produced contralateral turning in 6-OHDA lesioned rats. It is concluded that the apparent dopamine autoreceptor selectivity of TL-99 as assessed by in vivo animal test systems may be due partially to its alpha 2-agonist activity. The sedation and consequent reduction in mouse locomotor activity and in turning in the rat as the dose level is increased undoubtedly occurs via alpha 2-agonist and dopamine autoreceptor activity and cannot be interpreted as selectivity for the dopamine autoreceptor.     

Two simultaneously working storage pools of dopamine in mouse caudate and nucleus accumbens.

1. The dynamics of the decline of evoked dopamine overflow after repeated electrical stimulation (2 or 4 s train duration, 50 Hz) of the median forebrain bundle were investigated by means of in vivo voltammetry in mouse caudate and nucleus accumbens. An unexpected effect-slowing of the rate of dopamine decline after repeated stimulation at short (10 s or less) between-stimulation intervals, and an increase in the absolute amount of dopamine released at the beginning of the repeated stimulation-was found. 2. After the evoked dopamine overflow had been reduced by alpha-methyl-p-tyrosine (AMPT), repeated stimulation at intervals of 5 s increased dopamine release to each subsequent stimulation applied. 3. It is proposed that there are two compartments involved in dopamine storage. Both contribute to the release of dopamine, however, they may be separated artificially by either applying stimulation at short intervals or by depletion of intracellular dopamine. 4. The first releasable pool (newly synthesized, AMPT-sensitive) provides dopamine for the release after a single stimulation or repeated stimulation, being independent of whether the first stimulation is succeeded quickly by a second. It is also independent of between-stimulation interval. 5. The second pool (AMPT-insensitive storage pool) is progressively activated after repeated stimulation. The duration of the between-stimulation intervals is the crucial factor for the activation of this pool.     

Interaction of 1-methyl-4-phenylpyridinium ion and tyramine with a site putatively involved in the striatal vesicular release of dopamine.

The neurotoxin MPP+ potently inhibited the striatal binding of [3H]-tyramine, a putative marker for the vesicular transporter of dopamine, and provoked a massive in vivo release of striatal dopamine. Tetrabenazine, an established ligand for the vesicular catecholamine carrier, potently inhibited [3H]-tyramine binding, tyramine-provoked striatal efflux of dopamine and the fast component of MPP(+)-induced dopamine release. It is concluded that MPP+ in the striatum, besides interacting with additional intracellular targets, avidly binds at a vesicular site functionally involved with the outward transport of dopamine.     

THE METABOLIC FATE OF LEVODOPA IN MAN AND ANIMALS

SUMMARY 1. Administration of levodopa in man and rats resulted in a large increase in the daily excretion in the urine of dopamine and its metabolites, but not of noradrenaline.
2. In the rat administration of levodopa substantially increased dopamine concentrations in the heart and brainstem, but noradrenaline concentrations were decreased.
3. It is suggested that administration of levodopa leads to dopamine production in concentrations high enough to saturate intraneuronal uptake, so that the main uptake is extraneuronal, hence the major products are dopamine and its metabolites.
4. The lack of evidence of increased noradrenaline synthesis in the presence of diminished tissue levels of noradrenaline suggests that either the intraneuronal vesicular uptake or the β-hydroxylation of dopamine may be an important regulating step in the synthesis of noradrenaline.     

克拉霉素制剂研究应用进展

克拉霉素为半合成大环内酯类抗生素,是红霉素的衍生物,具有稳定性好,杀菌能力强,低pH 条件下易溶解,口服吸收好,不良反应少,患者耐受性高等优点。对多种革兰阳性或革兰阴性,需氧或厌氧菌均具很高的抗菌效果。由于克拉霉素具有水溶性差,味极苦的特性,使其临床应用受到限制,本文对克拉霉素制剂的研究现状进行了综述,以期为克拉霉素制剂的进一步研究提供参考。