丁螺环酮对小鼠主动和被动回避反应的影响

应用小鼠一次性被动回避和穿箱主动回避行为法 ,观察抗焦虑剂丁螺环酮 (Bus)对学习获得和记忆保持的影响 .结果发现 ,训练前 ip Bus0 .3- 1 0mg·kg-1不影响小鼠一次性被动回避反应的获得 ,但训练后立即 ip Bus 0 .3- 1 mg· kg-1时损害其保持 ,缩短小鼠进入暗室的潜伏期 .每天训练前 ipBus 0 .3- 1 0 mg· kg-1时 ,小鼠 d 1穿箱主动回避反应率显著提高 ,但随后的 d2 - 4,1 ,3,1 0 mg·kg-1组小鼠主动回避反应率显著降低 .Bus 0 .3-3.0 mg· kg-1不影响小鼠自发活动 ,1 0 mg· kg-1使小鼠活动性降低 ,这些结果表明 Bus不影响或促进学习获得 ,对记忆的保持具有损害作用     

HPLC-MS/MS测定人血浆中丁螺环酮浓度及人体药动学

 目的建立测定人血浆中丁螺环酮的LC-MS/MS方法,并用于缓释盐酸丁螺环酮胶囊的临床药动学试验。方法血浆样品经固相萃取后,以10mmol·L^-1的甲酸铵溶液-含0.5‰甲酸的乙腈溶液为流动相,梯度洗脱,经Symmetry C₁₈色谱柱(2.1mm×150mm,5μm)分离。通过电喷雾离子源,以多反应离子监测(MRM)方式进行检测。用于定量分析的离子反应分别为m/z 386→121.7(丁螺环酮)和409→237.7(内标,氨氯地平)。结果LC-MS/MS测定人血浆中丁螺环酮的线性范围为0.025～12.8μg·L^-1,r=0.9993。该方法的绝对回收率为74.97%～77.83%,相对回收率为93.67%～102.0%,日内、日间精密度(RSD)分别为0.9%～5.1%和1.9%～6.7%。在临床药动学研究中,应用此法测试了10名受试者口服盐酸丁螺环酮缓释胶囊后血浆中丁螺环酮的浓度。结论本法快速、准确,灵敏度高,重现性好,可以满足本试验低浓度药物测定及药动学研究要求。     

乌头汤加半夏不同炮制品对大鼠CYP3A的影响

目的:以乌头汤为载体,研究加入半夏不同炮制品后对大鼠细胞色素P450酶系(CYP)3A1/2的影响,为阐述"十八反"中半夏反乌头的反性内涵提供实验依据。方法:CYP3A酶活性采用体外温孵法和体内探针法进行检测,酶蛋白和mRNA表达采用蛋白质免疫印迹法(Western blot)和荧光定量聚合酶链式反应技术进行检测。结果:与乌头汤加生半夏组相比,乌头汤加法半夏各剂量组6β-羟基睾酮(6β-OH-Tes)生成速率未发生显著性变化,CYP3A蛋白表达显著增加(P0.01,P0.05),CYP3A1 mRNA的表达仅在0.60 g·kg~(-1)剂量组显著降低(P0.01);乌头汤加姜半夏在1.20 g·kg~(-1)剂量组时6β-OH-Tes生成速率极显著降低(P0.01),CYP3A蛋白表达仅在0.60 g·kg~(-1)剂量组明显增加(P0.05),CYP3A1 mRNA的表达在0.60,1.20 g·kg~(-1)剂量组有显著降低(P0.01);在体内探针法试验中乌头汤加法/姜半夏组6'-羟基丁螺环酮(6'-OHBP)和丁螺环酮(BP)的药时曲线下面积(AUC0-t)比值(6'-OH-BP/BP),1-(2-嘧啶基)哌嗪(1-PP)与BP的AUC0-t比值(1-PP/BP)均未发生明显变化。结论:不同半夏炮制品增强乌头汤对CYP3A的抑制作用的程度不同,这将会导致乌头汤中的双酯型生物碱类成分(如乌头碱)代谢减慢,从而引起药理作用的增强或毒性的增加。     

Characterization of the K current mediated by 5-HT1A receptor in the acutely dissociated rat dorsal raphe neurons

The action of 5-hydroxytryptamine (5-HT) via the 5-HT_1A receptor on dissociated rat dorsal raphe neurons was characterized under the whole-cell mode by using the nystatin-perforated patch-clamp technique. Under voltage-clamp conditions, 5-HT induced an inwardly rectifying K⁺ current (I_5-HT) in a concentration-dependent manner. I_5-HT was mimicked by 8-OH-DPAT and buspirone, which are both 5-HT_1A receptor agonists. I_5-HT was reversibly blocked by such 5-HT_1A receptor antagonists as (S)-UH-301 and spiperone but not by ketanserin, a 5-HT₂ receptor antagonist, granisetron, a 5-HT₃ receptor antagonist, and GR-113808, a 5-HT₄ receptor antagonist. I_5-HT was antagonized concentration-dependently by such K⁺ channel blockers as quinine, Ba²⁺ and 4-aminopyridine but was relatively insensitive to both Cs⁺ and tetraethylammonium. When the neurons were loaded with guanosine 5′-O-3-thiotriphosphate through a patch pipette, the K⁺ current induced by 5-HT became irreversible. N-ethylmaleimide (NEM), a sulfhydryl alkylating agent, irreversibly blocked I_5-HT. The intracellular perfusion with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), a Ca²⁺ chelator, or neomycine, a phospholipase C inhibitor, never significantly affected the 5-HT-induced response. 12-Myristate 13-acetate diester (PMA), a protein kinase C (PKC) activator, had only a weak inhibitory effect on I_5-HT, and staurosporine, a PKC inhibitor, failed to significantly occlude I_5-HT. Therefore, the K⁺ conductance activated via the 5-HT_1A receptor of dorsal raphe neurons was thus characterized by the sensitivity to such K⁺ channel blockers as quinine, Ba²⁺ and 4-aminopyridine. Moreover, G protein, which is NEM-sensitive and can couple to the 5-HT_1A receptor, is thus considered to activate the inwardly rectifying K⁺ conductance without being mediated by such second messengers as Ca²⁺ and PKC.     

多潘立酮联合丁螺环酮治疗功能性消化不良的临床对照研究

目的：探讨丁螺环酮治疗功能性消化不良的疗效及安全性。方法：将50例功能性消化不良患者随机分为两组,研究组27例,采用丁螺环酮5mg联合多潘立酮10mg,每天三次治疗;对照组23例,采用多潘立酮10mg,每天三次治疗,疗程均为4周。结果：在治疗的第四周末,研究组总有效率为81．48％,对照组为65．22％,两组比较差异有显著性（P〈0．05）。结论：多潘立酮联合丁螺环酮治疗功能性消化不良,疗效显著,安全性高。     

西酞普兰合并丁螺环酮治疗卒中后抑郁的疗效与安全性

目的：探讨西酞普兰合并丁螺环酮治疗卒中后抑郁的疗效与安全性。方法：脑卒中后抑郁患者60例随机分为观察组和对照组各30例,均服用西酞普兰20mg/d,2周内增至30-40mg/d;观察组同时加用丁螺环酮30mg/d。结果：与治疗前比较,治疗1周时,汉密顿抑郁量表（HAMD）评分,观察组即明显下降（P〈0.05）,治疗2周时对照组开始下降。治疗8周时,2组HAMD和中国卒中量表（CSS）评分均显著下降,日常生活活动能力量表（ADL）明显提高（P〈0.05或0.01）;与对照组比较,观察组HAMD、ADL改善更明显（P〈0.05）,副反应量表（TESS）则无差异。治愈显效率观察组优于对照组（83.3%、60%,P〈0.05）。结论：西酞普兰合并丁螺环酮能加强卒中后抑郁的治疗作用,且起效迅速,患者症状改善明显,显示出联合用药的优点。     

逍遥散加味联合丁螺环酮治疗广泛性焦虑症对照研究

目的探讨逍遥散加味联合丁螺环酮治疗广泛性焦虑症的临床疗效及安全性。方法将75例广泛性焦虑症患者随机分为两组,研究组37例,口服逍遥散加味汤剂联合丁螺环酮治疗;对照组38例,单用丁螺环酮治疗,观察8周。于治疗前及治疗1周、2周、4周、8周末采用焦虑自评量表、汉密顿焦虑量表评定临床疗效,副反应量表评定不良反应。结果治疗后两组焦虑自评量表、汉密顿焦虑量表评分均较治疗前显著下降,但研究组治疗各时段均较对照组下降更显著（P〈0．05或0．01）;治疗8周末研究组显效率73．0％、总有效率86．4％,对照组分别为50．0％、76．3％,研究组显效率显著高于对照组（x^2=4．17,P〈0．05）;研究组各项不良反应发生率均低于对照组。结论逍遥散加味联合丁螺环酮治疗广泛性焦虑症起效快,疗效显著,安全性高,依从性好,显著优于单用丁螺环酮治疗。     

舍曲林联合丁螺环酮治疗抑郁症伴性功能障碍对照研究

目的：探讨舍曲林联合丁螺环酮治疗抑郁症伴性功能障患者的临床疗效。方法将100例抑郁症伴性功能障碍患者随机分为两组,每组50例,两组均口服舍曲林治疗,观察组联合丁螺环酮合治疗,观察8周。采用汉密顿抑郁量表、抑郁自评量表评定抑郁状况,Olson婚姻质量问卷评定婚姻质量,性生活满意度量表评定性生活满意度。结果治疗后两组汉密顿抑郁量表、抑郁自评量表评分均较治疗前显著下降（P＜0．01）,观察组较对照组下降更显著（P＜0．01）;两组Olson婚姻质量问卷评分均较治疗前显著升高（P＜0．01）,观察组较对照组升高更显著（P＜0．01）;观察组性生活总满意率显著高于对照组（χ2＝7．48,P＜0．01）。结论舍曲林联合丁螺环酮治疗抑郁症伴性功能障患者效果显著,能显著提高患者的性生活满意度和婚姻质量,显著优于单用舍曲林治疗。     

Buspirone attenuates learned helplessness behavior in rats

Rats pretreated with either chlordiazepoxide (5 mg/kg) or buspirone (5 mg/kg) did not develop the shuttlebox escape deficit typically observed 24 hours after a session of inescapable tailshock. In contrast, the buspirone analog gepirone (MJ 13805) (2 or 5 mg/kg) did not block this shock-induced learning deficit. These results demonstrate that the nonbenzodiazepine anxiolytic buspirone, like chlordiazepoxide, attenuates the learned helplessness syndrome.