Effects of bromazepam on single-trial event-related potentials in a visual vigilance task

Thirty females performed a visual vigilance task under the influence of bromazepam (6 and 12 mg) in a placebo-controlled, double blind, experiment. Measures employed were percentage of hits, percentage of false alarms, response latency (RT), A (sensitivity), B (cautiousness), and RI (responsivity), as well as signal-and non-signal event-related potentials (ERPs). Bromazepam did not aggravate the normally occurring decrement in performance in vigilance tasks, but had an effect on overall level of performance: accuracy was reduced under the influence of the drug, but speed improved. A Drug×Period interaction for cautiousness (B) indicated increasingly less cautiousness with bromazepam, which probably contributed to faster motor responses (and more errors) than in the placebo group. The ERP data suggest that the effects of bromazepam are already manifest in the early stages of information processing (attention-detection) as mirrored by a drug effect on N1 amplitude. Deterioration at this early stage may affect later processing stages (P2–N2 amplitudes). As a result, subjects under the influence of the drug probably accumulate less signal evidence for their final evaluation.     

Residual effects of prolonged cannabis administration on exploration and DRL performance in rats

Chronic oral administration of cannabis extract to rats (daily ⁹ dose 20 mg/kg) was examined for its residual effect on open field activity and DRL (differential reinforcement of low-rate responding) performance, following a 2–3-month drug-free period. Locomotor activity during the latter part of an open field test was markedly increased in rats previously treated for either 6 months or 3 months with the drug. The same treatments also produced a significant impairment on a DRL-20 task relative to control subjects' performance. These and other findings (impaired maze learning and facilitated two-way shuttle box avoidance) might mean that cannabis produces long-lasting hippocampal, dysfunction in rats.     

Noradrenergic and dopaminergic interactions in escape behavior: Analysis of uncontrollable stress effects

The effects of norepinephrine receptor blockade on the deficits of escape behavior induced by haloperidol and by inescapable shock were evaluated. Phenoxybenzamine, the -norepinephrine receptor blocker, was found to enhance escape behavior and to eliminate the disruptive effects of both inescapable shock and haloperidol. In contrast, the -norepinephrine receptor antagonist, propranolol, was without effect on behavior under any of these conditions, while the dopamine--hydroxylase inhibitor, FLA-63, disrupted performance. Like phenoxybenzamine, the norepinephrine receptor stimulant, clonidine, was found to eliminate the behavioral disruption produced by haloperidol. These somewhat paradoxical findings were discussed in terms of the contribution of DA-NE interactions in determining behavioral change in aversive paradigms.     

Long-term l-Dopa pretreatment of mice: Central receptor subsensitivity or supersensitivity?

The effect of d-amphetamine added to the drinking water on the rate of conditioned lever pressing by rats was determined using fixed-ratio 30 (FR-30) and fixed-interval 2-min (FI-2) schedules of food presentation. After 32 days of gradual increase in drug concentration the average drug ingestion was 13 mg/kg/day. In tests with various doses of d-amphetamine injected before and after the chronic ingestion regimen, the rate-decreasing effects of d-amphetamine on FR responding were attenuated after chronic treatment, indicating development of a two- to three-fold tolerance. However, the rate-decreasing effect of d-amphetamine on FI responding was not altered by chronic ingestion. Since acute amphetamine treatment reduced the reinforcement frequency under the FR but not the FI schedule, these results are consistent with the hypothesis that a behavioral tolerance will develop most readily to drug effects that decrease the frequency of reinforcement. Upon removal of d-amphetamine from the drinking water there was some increase in the rate of FR responding, but no change in FI responding.     

多西环素肠溶微粒胶囊与片剂的人体生物等效性

目的 :研究多西环素肠溶微粒胶囊和多西环素片的人体生物等效性与药动学。方法 :2 0名男性健康志愿者随机分 2组 ,按双周期交叉口服单剂量 2 0 0mg多西环素的 2种制剂 ,分别于服药前及服药后 0 5 ,1,1 5 ,2 ,2 5 ,3,4,6 ,8,12 ,2 4,48,72h取血样 ,以HPLC法测定血浆中多西环素浓度 ,计算 2种制剂相对生物利用度参数 ,并评价其生物等效性。结果 :口服受试制剂多西环素肠溶微粒胶囊和参比制剂多西环素片的药动学参数 :cmax分别为 (3 6 5± 0 81) μg·mL-1和 (3 6 5± 0 73) μg·mL-1,tmax分别为 (2 5± 0 3)h和 (2 2± 0 7)h ,T1/ 2 (消除半衰期 )分别为 (2 1 4 8± 3 2 0 )h和 (2 1 85± 3 11)h ,AUC0→ 72 分别为 (72 18±2 2 6 8) μg·h·mL-1和 (72 0 6± 2 1 0 8) μg·h·mL-1,AUC0→∞ 分别为 (81 4 4± 2 4 94) μg·h·mL-1和 (81 82± 2 3 19) μg·h·mL-1,多西环素肠溶微粒胶囊相对生物利用度为 (10 1 9± 2 5 2 ) %,对参数cmax,AUC0→ 72 先进行方差分析 ,再进行双单侧t检验 ,表明 2种制剂的参数生物等效 ,tmax经非参数检验表明无统计学差异。结论 :多西环素肠溶微胶囊和多西环素片具有生物等效性。     

高效液相色谱法测定进口芦荟药材中芦荟苷的含量

目的 :建立了测定进口药材芦荟中芦荟苷含量的高效液相色谱法。方法 :采用高效液相色谱法 ,以ZORBAXSB-C₁₈(4.6mm× 2 50mm ,5μm)为色谱柱 ,流动相乙腈 水 (25∶75) ,检测波长 355nm ,流速 1.0mL·min^-1 。结果 :芦荟苷在 0.17～5.9μg线性关系良好 ,r=0.9999,芦荟苷平均加样回收率为 98.6% ,RSD 1.32 %(n =6)。结论 :试验结果表明 ,该方法准确、灵敏度高 ,重现性好。     

RP-HPLC测定犬血浆中卡托普利

目的　采用反相高效液相色谱法测定犬血浆中卡托普利浓度。方法　以对溴苯乙酰基溴为衍生剂 ,血浆样品经衍生反应后 ,用乙酸乙酯 -苯 (1∶1)提取 ,以ODSC18为固定相 ,乙腈∶水∶冰醋酸 (4 5∶5 5∶0 2 )为流动相 ,UV2 5 8nm紫外检测。结果　在 2 5～ 6 0 0 μg·L-1浓度范围线性良好 ,最小检测浓度为 12 5 μg·L-1。其日内差及日间差RSD分别小于 4 95 %和 2 88% ,相对回收率大于 94 8%。结论　方法简便灵敏 ,为卡托普利样品分析及临床药物监测提供了检测方法。     

地西泮代谢物的结合物水解条件研究

目的:考察β 葡萄糖醛酸苷酶水解尿液中地西泮代谢物的结合物的酶解条件.方法: 实验设计采用正交表L9(34).取尿样2 mL,加内标,再加不同量的β 葡萄糖醛酸苷酶,在不同温度、不同酶解时间下水解,然后用正己烷 二氯甲烷(5∶3)5 mL提取,挥干提取液后用50 μL甲醇溶解,10 μL进样,采用高效液相色谱法检测.结果:对水解产物峰面积与内标物峰面积的比值进行方差分析,发现水解尿液中去甲地西泮、替马西泮、奥沙西泮的葡萄糖醛酸苷结合物的最佳酶解条件分别为55℃,5 h,5 000 U酶量;55℃,2 h,1 000 U酶量;55℃,2 h,5 000 U酶量.结论:水解2 mL尿液中地西泮代谢物的结合物的最佳条件为55℃,5 h,5 000 U酶量.     

芦氟沙星胶囊的人体药动学研究

目的:测定盐酸芦氟沙星胶囊在人体内的药动学参数,为临床合理用药提供依据.方法:6例健康志愿者口服盐酸芦氟沙星胶囊200 mg后于不同时间取血,用高效液相色谱法(HPLC)测定血浆中芦氟沙星的血药浓度,按3P87药动学程序处理.结果:盐酸芦氟沙星胶囊口服后符合血管外口服一室开放模型,Tmax为(1.53±0.34) h,Cmax为(1.93±0.41) mg•L 1,浓度 时间曲线下面积(AUC)为(99.67±10.71) mg•h•L 1,t1/2为(34.16±8.55) h.结论:芦氟沙星血药浓度高,组织分布广,具有良好的药动学特征.