HPLC 法测定盐酸雷诺嗪在不同种属血浆中的蛋白结合率

目的：研究盐酸雷诺嗪与不同种属血浆的蛋白结合情况。方法采用高效液相色谱法（ HPLC法）和平衡透析法测定管状半透膜内的血浆药物浓度及管状半透膜外的缓冲液中药物浓度,并计算蛋白结合率。结果盐酸雷诺嗪在不同种属血浆（大鼠血浆、人血浆和牛血清白蛋白）中的蛋白结合率均大于50％,分别为：大鼠血浆：（63．43±1．9）％;人血浆：（61．58±4．1）％;牛血清白蛋白：（62．16±2．9）％。且盐酸雷诺嗪在各种属血浆中最低定量下限均为0．05 mg/L。结论盐酸雷诺嗪在不同种属血浆（大鼠血浆、人血浆和牛血清白蛋白）中的蛋白结合率及蛋白结合药物的表观最大能力均较高。随着药物血浆浓度升高,盐酸雷诺嗪结合率升高,有较强的浓度依赖性。     

微透析法测定青藤碱大鼠体外血浆蛋白结合率

微透析法（microdialysis，MD）是新型药物动力学采样方法，可在活体动物身上进行实时（realtime）、动态（dynamic state）采样，所采集的样品不需前处理可直接进样分析。但此法对于高分子量、高蛋白结合率和高脂溶性的药物不适宜进行药物动力学研究。青藤碱是一种具有抗风湿活性的弱亲脂性生物碱，为了采用微透析法研究青藤碱的大鼠药物动力学行为，有必要测定大鼠的体外血浆蛋白结合率来评价体内微透析采样的可行性。     

重组人甲状旁腺素类似物PTH（1-34）在大鼠体内药动学研究

目的：研究大鼠scPTH（1-34）的药动学特征。方法：用125I标记PTH（1-34）示踪法对大鼠scPTH（1-34）后的血清药物浓度进行了测定,并用3P97程序拟和分析并计算药动学参数,采用超滤离心的方法进行药物与血浆蛋白结合率的研究。结果：大鼠scPTH（1-34）10、20和40μg/kg后,药物消除符合一房室模型。平均t1/2ke为（0.92±0.04）h;平均CL为（0.56±0.05）L/（kg.h）;Cmax和AUC0-8h均与剂量呈线性正相关,不同剂量药物与血浆蛋白平均结合率为13.4%。结论：大鼠scPTH（1-34）后,药物消除符合线性动力学特征。     

抗生素药物血浆蛋白结合率的定量构动关系

目的 应用人工神经网络方法对61种抗生素进行药物分子结构和药物血浆蛋白结合率的定量结构—药物动力学关系的研究(QSPR)。方法 建立了含一个隐含层的反传神经网络，输出层为实验获得的药物血浆蛋白结合率；输入层为计算获得的药物分子的理化参数，量化参数和分子连接性指数等药物分子结构参数。为了验证网络训练结果，随机挑选51个药物为训练集，进行了1eave—one—out分析。结果 最后利用挑选剩下的10个药物进行预测，其血浆蛋白结合率的预测值能很好地与实验数据相吻合。结论所建立的神经网络模型能够有效地进行药物血浆蛋白结合率与药物分子结构的相关性分析。同时也证明了人工神经网络功能强大，将成为药物QSPR研究的一个有效工具。     

二-（2,4-二氯苯甲酰异羟肟酸）二苯基合锡大鼠血浆蛋白结合率的测定

目的建立二-（2,4-二氯苯甲酰异羟肟酸）二苯基合锡（DPDCT）在大鼠血浆中蛋白结合率的测定方法。方法采用HPLC法测定大鼠血浆中药物总浓度及游离药物浓度,结合平衡透析法测定血浆蛋白结合率。结果 DPDCT在质量浓度为0.2、1.0、5.0μg/mL时与大鼠的血浆蛋白结合率分别为（58.9±2.0）%、（57.4±1.2）%和（58.6±0.8）%。不同浓度组血浆蛋白结合率差异无统计学意义。结论该方法灵敏度高,重复性好,操作简单,能够满足生物样品分析的要求。DPDCT具有中等强度的血浆蛋白结合率。     

气相色谱法测定甘草酸α体、β体及其苷元的人血浆蛋白结合率

目的研究甘草酸立体异构体及其苷元的血浆蛋白结合率。方法用气相色谱法测定人血浆中甘草酸立体异构体（α体和β体）及其苷元的浓度，并计算蛋白结合率。结果当血浆浓度大于50％时．α体的血浆蛋白结合率大于β体；血浆浓度小于50％时．α体的血浆蛋白结合率小于β体。而苷元的血浆蛋白结合率始终是α体小于β体。结论甘草酸立体异构体及其苷元在不同浓度血浆中的蛋白结合率存在差异。     

二-(2, 4-二氯苯甲酰异羟肟酸) 二苯基合锡大鼠血浆蛋白结合率的测定

目的 建立二-(2, 4-二氯苯甲酰异羟肟酸) 二苯基合锡（DPDCT）在大鼠血浆中蛋白结合率的测定方法。方法 采用HPLC法测定大鼠血浆中药物总浓度及游离药物浓度,结合平衡透析法测定血浆蛋白结合率。结果 DPDCT在质量浓度为0.2、1.0、5.0 μg/mL时与大鼠的血浆蛋白结合率分别为（58.9±2.0）%、（57.4±1.2）%和（58.6±0.8）%。不同浓度组血浆蛋白结合率差异无统计学意义。结论 该方法灵敏度高,重复性好,操作简单,能够满足生物样品分析的要求。DPDCT具有中等强度的血浆蛋白结合率。     

高效毛细管电泳/前沿分析及其在手性药性药物-蛋白结合研究中的应用

目的：综述了高效毛细管电泳／前沿分析（HPCE／FA）方法的原理、特点、及其在手性药物－蛋白结合研究中的应用。方法：采用HPCE／FA方法。结果：不同的手性药物对映体与蛋白结合可能存在判别,同一药物对映体之间与不同蛋白结合率可能存在差别,HPCE／FA仅需极少量样品即可同时测定手性药物各对映体在蛋白结合中的游离浓度。结论：HPCE／FA是一种高效、分析迅速、样本用量极少的研究蛋白结合方法,特别是对于手性药物与昂贵不易获得的蛋白结合研究。     

F1013人血浆蛋白结合率测定及其影响因素

目的测定新Caspase抑制药F1013的人血浆蛋白结合率，并考察影响测定的因素。方法采用高效液相色谱法测定不同条件下超滤分离的游离药物浓度。结果amicon Ultra 0.5超滤装置（Millipore）操作性较强，可较好地运用于血浆蛋白结合率研究；随离心速率、超滤时间递增，人血浆游离药物浓度逐渐增高，直至稳定；随温孵时间递增，人血浆游离药物浓度逐渐减小，直至稳定。采用超滤法测定F1013人血浆蛋白结合率过程中，离心速率、超滤时间和温孵时间均对结果产生重要影响。经过优化和筛选，最佳超滤条件为采用超滤法测定F1013人血浆蛋白结合率，将含药血浆于37 ℃水浴温孵1 h，置Amicon Ultra 0.5超滤装置，14 000 r•min－1离心15 min。结论HPLC法测定回收率、精密度均符合要求，具较好的可行性。超滤法测F1013平均人血浆蛋白结合率约为52%。     

国产阿齐红霉素在大鼠的组织分布及与正常人血浆蛋白结合率研究

对阿齐红霉素在大鼠的组织分布及与正常人血浆蛋白结合率进行研究，结果表明：阿齐红霉素在体内能很快分布于大多数脏器和组织中，并较长时间内保持较高的药物浓度。蛋白结合率测定结果表明：阿齐红霉素是一种血浆蛋白结合率较低的药物。     

CHARACTERIZATION OF BINDING SITES FOR [3H]-IDAZOXAN, [3H]-P-AMINOCLONIDINE AND [3H]-RAUWOLSCINE IN THE KIDNEY OF THE DOG

1. We characterized the binding of [³H]-rauwolscine, [³H]-p-aminoclonidine and [³H]-idazoxan in a dog kidney membrane preparation. Our aim was to determine the pharmacological nature of the α₂-adrenoceptor- and imidazoline-preferring binding sites in this organ. 2. [³H]-Rauwolscine bound to an apparent single site with an affinity (K_D) of 2.2 nmol/ L and a maximum density (B_max) of 58.5 fmol/mg protein, when 10 μmol/L idazoxan defined non-specific binding. However displacement studies demonstrated that a number of compounds, including prazosin, inhibited [³H]-rauwolscine binding in a complex manner consistent with displacement from two distinct binding sites. The majority (69%) of the [³H]-rauwolscine binding sites had a relatively low affinity for prazosin (K_I= 398 nmol/L), while the remainder had a relatively high affinity for prazosin (K_I= 7.9 nmol/ L). 3. [³H]-p-Aminoclonidine bound to an apparent single site (K_D= 5.2 nmol/L; B_max= 72.4 fmol/mg protein), when 10 μmol/L phentolamine defined non-specific binding. When 1 μmol/L of the potent and selective α₂-adrenoceptor antagonist 2-methoxyidazoxan was included in the incubate, no specific binding was detected. We therefore conclude that under the conditions of this experiment [³H]-p-aminoclonidine binds only to α₂-adrenoceptors in the dog kidney. 4. [³H]-Idazoxan bound to two sites, with a higher (K_D= 0.95 nmol/L; B_max= 43.9 fmol/mg protein) and lower (K_D= 9.1 nmol/L; B_max= 93.8 fmol/mg protein) affinity, respectively, when 1 mmol/L phentolamine defined non-specific binding. When 10 μmol/ L GTPγS was included in the incubate, the low affinity site was unaffected but the maximum binding at the higher affinity site was reduced by 79%. 2-Methoxyidazoxan displaced [³H]-idazoxan in a monophasic manner and with low potency (IG₅₀=11.5 μmol/L). Yohimbine, efaroxan, clonidine, rilmenidine, guanabenz and idazoxan itself displaced [³H]-idazoxan in a complex manner; the slope of the displacement curves being less than unity. 5. We conclude that the dog kidney contains a heterogeneous population of α₂-adrenoceptors that can be labelled either with [³H]-rauwolscine or [³H]-p-aminoclonidine. The dog kidney also contains a heterogeneous population of non-adrenoceptor imidazoline-preferring binding sites of the I₂-subtype, that can be labelled with [³H]-idazoxan. The binding site for which [³H]-idazoxan has the highest affinity appears to be coupled to a guanine nucleotide binding regulatory protein.     

柱切换HPLC法测定豚鼠体内诺氟沙星银解离物诺氟沙星的浓度

用柱切换HPLC法建立了豚鼠血浆和皮下组织液中诺氟沙星银体内主要解离物诺氟沙星的测定方法。预处理柱为μ-BondapakC₁₈,37～50μm,50mm×5mmID;分析柱为YWG-C₁₈,10μm,150mm×5mmID。预处理流动相为0.008mo1/L磷酸缓冲液,流速为3ml/min;分析流动相为甲醇—0.008mol/L磷酸缓冲液—0.05mol/L四丁基溴化铵(25:75:4)。紫外检测波长为280nm。皮下组织液及血浆中的线性范围分别为100～3200ng/ml(r=0.9999)和2～128μg/ml(r=0.9999);最低检测浓度分别为10ng/ml和0.25μg/ml,方法的平均回收率为102%,日内及日间偏差均小于7%。     

大鼠心肌质膜[~3H]forskolin结合部位的特征(英文)

近年来从植物研究中发现的一种二萜衍生物(forskolin)是一种新型作用于心血管系统的药物。质膜中forskolin结合部位被认为是腺苷酸环化酶(EC4.6.1.1.)的催化亚单位。我们已经证明了它对大鼠心肌质膜腺苷酸环化酶的激活作用呈剂量效应相关。本文用〔1,2-~3H〕forskolin研究了大鼠心肌质膜for-skolin结合部位的特征。实验结果表明:〔~3H〕forskolin结合量和膜蛋白呈线性相关;其特异结合是快速的、可饱和的、可逆的、依赖温度的;结合反应的平衡解离常数(Ka)为0.21±SD 0.08μmol/L,其最大结合浓度为3.3±SD1.2 pmol/mg蛋白,Hill系数为1.07±SD0.05;37℃时缔合速率常数为0.0013(nmol/L)~(-1)·min~(-1),30 min达到平衡状态;心肌质膜结合的〔1,2-~3H〕forskolin被forskolin取代的解离速率常数:37℃时为0.22 min~(-1)(t_(1/2)=3.2 min),0℃时为0.03 min~(-1)(t_(1/2)=25.8min),IC_(50)为1.6μmol/L。本文实验结果提示:心肌质膜〔~3H〕forskolin结合分析可以作为研究激素和药物对心肌腺苷酸环化酶催化亚基作用的良好模型。     

[3H]2-(2-Benzofuranyl)-2-imidazoline,a highly selective radioligand for I2-imidazoline receptor binding sites Studies in rabbit kidney membranes

2-(2-Benzofuranyl)-2-imidazoline (2-BFI) has recently been characterised as a selective ligand for the I₂-type of imidazoline-receptor binding site(s) (I₂-RBS). The present studies determined the relative levels of specific [³H]2-BFI binding to membrane homogenates of brain and kidney from rat, guinea pig and rabbit and identified the pharmacological characteristics of [³H]2-BFI binding sites in rabbit kidney membranes. Rabbit kidney membranes had the highest relative density of specific [³H]2-BFI binding of all tissues studied (2000?fmol/mg protein). Rabbit brain and guinea pig kidney had moderate levels of specific [³H]2-BFI binding (350–500?fmol/mg protein), while rat kidney and guinea pig and rat brain displayed much lower densities of binding (40–65?fmol/mg protein). Studies of [³H]2-BFI binding kinetics in rabbit kidney homogenates revealed binding to two distinct sites with K _d values of 0.10?±?0.01?nmol/l and 1.00?±?0.36?nmol/l respectively. Equilibrium saturation studies were also consistent with the presence of two binding sites – [³H]2-BFI (0.01–20?nmol/l) bound to sites with affinities of 0.10?± 0.01?nmol/l and 0.92?±?0.13?nmol/l and binding densities of 470?±?80 and 840?±?60?fmol/mg protein (n=3), representing 36 and 64% respectively. Drug inhibition studies revealed that l-adrenaline; α₁-adrenoceptor drugs (prazosin, l-phenylephrine) and α₂-adrenoceptor drugs (rauwolscine, methoxyidazoxan, 2-(2,4-(O-methoxyphenyl)-piperazin-1-yl)-ethyl-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione (ARC-239) had extremely low affinities for [³H]2-BFI binding sites (IC₅₀?≥?10?μmol/l). Putative I₁-RBS compounds, p-aminoclonidine, moxonidine, imidazole-4-acetic acid and cimetidine, inhibited [³H]2-BFI binding to rabbit renal membranes with low to very low affinities (K _i values 3 to ≥100?μmol/l), suggesting [³H]2-BFI does not label I₁-RBS in rabbit kidney membranes. I₂-RBS compounds – 2-(4,5-dihydroimidaz-2-yl)-quinoline (BU224), 2-(4,5-dihydroimidaz-2-yl)-quinoxaline (BU239), idazoxan and cirazoline – potently inhibited [³H]2-BFI binding (K _i values 0.37–1.6?nmol/l), confirming the labelling of I₂-RBS. Inhibition of [³H]2-BFI binding by certain compounds was consistent with their interaction with two binding site populations – for example (drug, K _i values) guanabenz, 0.65?nmol/l and 0.17?μmol/l; naphazoline, 0.94?nmol/l and 2.8?μmol/l; amiloride, 76?nmol/l and 26?μmol/l rilmenidine, 150?nmol/l and 50?μmol/l; and clonidine, 230?nmol/l and 70?μmol/l. The high affinity of amiloride for a high proportion (85%) of the binding is consistent with the presence of the I_2A-subtype of I-RBS in rabbit kidney. These results demonstrate that [³H]2-BFI is a highly selective and high affinity radioligand for I₂-RBS which should be useful for the further characterisation of these sites in mammalian tissues.     

八肽胆囊收缩素对[~3H]埃托啡与大鼠脑阿片受体结合的抑制作用

本实验观察了CCK—8对[~3H]Et与大鼠脑阿片受体结合的影响.含硫CCK—8能抑制[~3H]Et与高亲和位点的结合,使K_D值增大(P<0.001),B_(max)减小(P<0.01),在10 fmol/L～Lμmol/L范围内呈量效关系.但对低亲和位点的结合没有影响.无硫CCK—8仅对[~3H]Et高亲和位点的K_D值有较小程度的增大(P<0.05),不影响B_(max)值.CCK—8(10 nmol/L)抑制[~3H]Et与阿片受体结合的作用能被CCK受体拮抗剂谷丙酰胺(1μmol/L)所阻断.结果提示,CCK—8可能通过激活CCK受体发挥对阿片受体的抑制作用。     

Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10–30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE₂₅, MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25?min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711?μg h/mL and 137.518?μg/mL in comparison to 321.011?μg h/mL and 38.673?μg/mL for AUC and Cp_max, respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.     

ROLE OF INTRACELLULAR SIGNALLING PATHWAYS IN HYDROGEN PEROXIDE-INDUCED INJURY TO RAT GLOMERULAR MESANGIAL CELLS

1. Brief exposure of cultured rat glomerular mesangial cells (GMC) to H202 in nominally bicarbonate-free solution induced a rapid dose dependent, dantrolene-inhibitable increase in intracellular free Ca²⁺ from 65 ± 6 to 203 ± 14 nmol/L and a prolonged release of [¹⁴C]-arachidonic acid [¹⁴C]-AA which preceded the onset of cell membrane damage assessed by trypan-blue uptake. 2. Ca²⁺ responses were potentiated in HCO₃^?/CO₂ containing buffers and reached values of 1145 ± 100 nmol/L at 1 mmol/L H₂O₂. In HCO₃^?/CO₂ solutions, but not HEPES buffer, HzOz-induced Ca²⁺ increases were markedly attenuated by verapamil (100 μmol/L) or removal of extracellular calcium. 3. Enhanced release of [¹⁴C]-AA was partially attenuated by inhibitors of key intracellular signalling mechanisms including the phospholipase-A₂ (PLA₂) inhibitor mepacrine (100 μmol/L), the NADPH oxidase inhibitor diphenyliodonium (10 μmol/L), the mitochondrial calcium-cycling inhibitor ruthenium red (100 μmol/L) and the iron chelator dipyridyl (100 μmol/L). Release was unaffected by protein kinase C inhibition with H7 (100 μmol/L), inositol triphosphate antagonism with neomycin (1 mmol/L) or overnight treatment with the G-protein antagonist pertussis toxin (5 μg/mL). 4. Several structurally diverse lipoxygenase inhibitors, including esculetin, baicalein and phenidone, over the dose range 1–100 μmol/L, also prevented [¹⁴C]-AA release and markedly protected against cell membrane damage. No drug directly scavenged H202 assessed by UV absorption. 5. These results indicate that H₂O₂ activates in GMC a complex series of interrelated pathological mechanisms which in turn contribute to a prolongation of oxidative damage beyond the time of the initial exposure. These include an increase in intracellular calcium which, depending upon conditions, appears to be mediated by release from intracellular stores as well as Ca²⁺ entry from the extracellular space. In turn there is a sustained release of arachidonic acid, which may partly depend on prolonged activation of PLA₂ but not phospholipase C. 6. Release of [¹⁴C]-AA could be attenuated by inhibitors of NADPH oxidase, mitochondrial calcium-cycling, iron chelators and a structurally diverse range of lipoxygenase inhibitors in association with protection from H₂Otrnediated cell membrane damage.     

Vasorelaxation induced by methyl cinnamate,the major constituent of the essential oil of Ocimum micranthum,in rat isolated aorta

The aim of the present study was to investigate the vascular effects of the E‐isomer of methyl cinnamate (E‐MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1–3000 μmol/L, E‐MC concentration‐dependently relaxed endothelium‐intact aortic preparations that had been precontracted with phenylephrine (PHE; 1 μmol/L), with an IC₅₀ value (geometric mean) of 877.6 μmol/L (95% confidence interval (CI) 784.1–982.2 μmol/L). These vasorelaxant effects of E‐MC remained unchanged after removal of the vascular endothelium (IC₅₀ 725.5 μmol/L; 95% CI 546.4–963.6 μmol/L) and pretreatment with 100 μmol/L N^G‐nitro‐l ‐arginine methyl ester (IC₅₀ 749.0 μmol/L; 95% CI 557.8–1005.7 μmol/L) or 10 μmol/L 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (IC₅₀ 837.2 μmol/L; 95% CI 511.4–1370.5 μmol/L). Over the concentration range 1–3000 μmol/L, E‐MC relaxed K⁺‐induced contractions in mesenteric artery preparations (IC₅₀ 314.5 μmol/L; 95% CI 141.9–697.0 μmol/L) with greater potency than in aortic preparations (IC₅₀ 1144.7 μmol/L; 95% CI 823.2–1591.9 μmol/L). In the presence of a saturating contractile concentration of K⁺ (150 mmol/L) in Ca²⁺‐containing medium combined with 3 μmol/L PHE, 1000 μmol/L E‐MC only partially reversed the contractile response. In contrast, under similar conditions, E‐MC nearly fully relaxed PHE‐induced contractions in aortic rings in a Ba²⁺‐containing medium. In preparations that were maintained under Ca²⁺‐free conditions, 600 and 1000 μmol/L E‐MC significantly reduced the contractions induced by exogenous Ca²⁺ or Ba²⁺ in KCl‐precontracted preparations, but not in PHE‐precontracted preparations (in the presence of 1 μmol/L verapamil). In addition, E‐MC (1–3000 μmol/L) concentration‐dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E‐MC‐induced endothelium‐independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca²⁺ influx through voltage‐dependent Ca²⁺ channels. However, the involvement of a myogenic mechanism in the effects of E‐MC is also possible.     

The β3-adrenoceptor agonist SR58611A inhibits gastric acid secretion in the conscious cat

The effect of the β₃-adrenoceptor agonist {N-[(2S)-7-ethoxycarbonyl-methoxyl-1, 2, 3, 4-tetrahydro-naphth-2-yl] (2R)-2-(3-chloro-phenyl)2-hydroxyethanamine hydrochloride} (SR58611A) on gastric acid secretion was investigated in conscious cats with a gastric fistula. Intravenous infusion of SR58611A (0.3–3μmol/kg/h) caused a dose-dependent inhibition of the acid secretion stimulated by 2-deoxy-D-glucose (2DG), with a maximum reduction by 45%. The secretory effect of the histamine H₂-receptor agonist dimaprit only tended to be reduced by SR58611A (3μmol/kg/h). The inhibitory effect of SR58611A was not modified by the non selective β₁- and β₂-adrenoceptor antagonist propranolol (1.5μmol/kg i.v.), but it was prevented by bupranolol (10μmol/kg i.v.), a drug endowed with β₃-antagonistic properties. Both antagonists blocked the inhibitory effect of the β₂-adrenoceptor agonist clenbuterol (0.1μmol/kg/h) on 2DG-induced acid secretion. These findings suggest that compound SR58611A inhibits gastric acid secretion in the conscious cat through activation of β₃-adrenoceptors insensitive to propranolol.     

赛庚啶对氧自由基的清除作用

赛庚啶(Cyp)对Fenton反应生成的·OH有较强的直接清除作用(EC₅₀为54μmol/L),并明显抑制·OH的生成速率(IC₅₀为22 μmol/L),且作用明显比·OH特异性清除剂甘露醇强(其EC₅₀和IC₅₀分别为22.7 mmol/L和10.7mmol/L)。Cyp对大鼠腹腔多形核白细胞(PMNs)产生的O₂也有一定的清除作用,其IC₅₀为179 μmol/L。提示Cyp的抗心肌损伤作用可能至少部分与其清除氧自由基作用相关。