Effects of Corydalis yanhusuo and Angelicae dahuricae on cold pressor-induced pain in humans: a controlled trial

Pain is considered the most common complaint worldwide for which patients seek treatment. Conventional analgesic agents play an important role in modern pain therapy, but they cause several adverse effects. Therefore, newer and better analgesics continue to be investigated. In this controlled clinical trial, the authors evaluated the analgesic effects of 2 herbal medicines, Corydalis yanhusuo and Angelicae dahuricae. They used the cold-pressor test-a simple, reliable, and widely used model in humans-for induction of tonic pain. They demonstrated that after a single, oral administration of the extracts of C. yanhusuo and A. dahuricae, the pain intensity and pain bothersomeness scores significantly decreased (both P < .01). Dose-related analgesic effect was also observed. Results from this study suggest that C. yanhusuo and A. dahuricae may have a potential clinical value for treating mild to moderate pain.     

Modulation of pain perception by ramipril and losartan in human volunteers

The angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are a well known entity and have been used in therapeutics for various indications like hypertension, myocardial infarction and CHF. However, there is a renewed interest in these compounds in terms of their effects on pain perception in animals as well as in human beings. They have yielded contradictory results, showing hyperalgesia in some studies but analgesia in others. Hence this study was undertaken to evaluate the effect of Ramipril (an ACE-I) and Losartan (an ARB) on pain perception in human volunteers using cola caps and handcuff of sphygmomanometer. A total of 30 healthy, normotensive individuals with no previous history of intake of analgesics during or 4 weeks prior to the study were selected after an informed consent. The first group received a single dose of placebo, the second group received Ramipril (2.5 mg) & the third group received Losartan (50 mg). Pain perception threshold (the point at which an individual first experiences pain) and the maximum tolerated pain were assessed using the above method. The control group showed no significant changes in pain threshold, but the group receiving either Ramipril or Losartan showed a decline in threshold for maximum tolerated pain. Only Ramipril and not Losartan decreased the pain perception threshold. Our study revealed that single dose treatment of healthy volunteers with Ramipril and Losartan may cause algesia as early as after ingestion of the first dose and further studies are needed to study their long term effects on pain perception.     

Lidocaine and cardiovascular reflex responses to simulated orthostatic stress in normal volunteers.

The interactions of lidocaine with baroreceptor reflexes during simulated orthostatic stress or moderate volume depletion were investigated in healthy volunteers using the lower body negative pressure (LBNP) test. Cardiopulmonary baroreceptors were selectively unloaded at low levels of LBNP (-15 mm Hg) since the central venous pressure (CVP) decreased (-1.4 +/- 0.3 mm Hg) without changes in arterial pressure (AP) and heart rate (HR) but significant increases in forearm vascular resistance (FVR) and plasma noradrenaline (PNA). Cardiopulmonary as well as arterial baroreflexes were both unloaded at higher levels of LBNP (-40 mm Hg) since the CVP (-3.4 +/- 0.4 mm Hg) and systolic AP (-10 +/- 3 mm Hg) decreased whereas FVR, PNA, and plasma renin activity (PRA) increased further (all p less than 0.05). Following lidocaine infusion (serum level of 3.8 +/- 0.2 micrograms/ml), the AP, HR, FVR, and PNA increased and CVP decreased (p less than 0.05). Compared to LBNP performed under saline, lidocaine did not alter the LBNP (-15 mm Hg)-induced changes in cardiovascular and biological parameters but significantly decreased the induced rises in HR, FVR, PNA, and PRA at a LBNP of -40 mm Hg (p less than 0.05). In an additional study, it was also demonstrated that lidocaine significantly decreased the sensitivity of the reflex-mediated bradycardia following phenylephrine injection and attenuated the vasoconstrictor response to the cold pressor test taken as a nonspecific somatic pressor reflex.(ABSTRACT TRUNCATED AT 250 WORDS)     

The countering of diazoxide-induced vasodilatation by tenoxicam in normal volunteers

The effect of the nonsteroidal anti-inflammatory drug, tenoxicam, on diazoxide-induced lowering of standing diastolic blood pressure was explored in 10 normal volunteers.With diazoxide there was a significant fall in the 5-min standing diastolic pressure, i.e. a median drop of 15.5, 11.0, 9.5 and 7.0 mm Hg at 10, 35, 75 and 105 min, respectively, but with the tenoxicam-diazoxide regimen this pressure did not differ significantly from baseline at any time point. Tenoxicam did not modify the diazoxide-induced changes in blood glucose and plasma insulin.It may be that prostaglandins normally contribute to the lowering of peripheral vascular resistance, or that acutely-administered diazoxide enhances the release of vasodilatory prostaglandins.     

Psychoactivity of atropine in normal volunteers

Subjective effects of atropine sulfate injections were assessed in normal volunteers (n = 10), as one portion of a 3-part study (behavioral, subjective and physiologic effects of atropine). Each volunteer was given 0, 2 or 4 mg/70 kg atropine sulfate intramuscularly according to randomized block sequences on different test days. To assess psychoactivity of atropine, the Single Dose Questionnaire (SDQ) and the Addiction Research Center Inventory (ARCI) were given 1 hr before and 1 hr following drug injections. Data from the SDQ indicated that atropine produced significant discriminable effects but did not elevate scores on a drug liking scale. Data from the ARCI indicated that atropine produced significant sedative-like effects (pentobarbital-chlorpromazine-alcohol scale). Taken together, the data from the psychometric instruments confirms that atropine is a drug of relatively low abuse potential.     

Modulation of lipopolysaccharide-induced oxidative stress by capsaicin

This study investigated the effect of capsaicin (the active principle of hot red pepper and a sensory excitotoxin) on oxidative stress after systemic administration of the endotoxin lipopolysaccharide (100?μg/kg, i.p.) in rats. Capsaicin (15, 150 or 1,500?μg/kg; 10, 100 or 400?μg/mL) was given via intragastric (i.g.) or intraperitoneal (i.p.) routes at time of endotoxin administration. Rats were killed 4?h later. Malondialdehyde (MDA) and reduced glutathione (GSH) were measured in brain, liver, and lungs. Alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase (ALP), nitric oxide, and glucose were measured in serum. In addition, histopathological examination of liver tissue was performed. In LPS-treated rats, hepatic GSH increased significantly by 40.8% after i.p. capsaicin at 1,500?μg/kg. Liver MDA increased significantly by 32.9% after the administration of i.g. capsaicin at 1,500?μg/kg and by 27.8 and 37.6% after the administration of i.p. capsaicin at 150 and 1,500?μg/kg, respectively. In lung tissue, both MDA and GSH were decreased by capsaicin administration. MDA decreased by 19-20.8% after i.g. capsaicin and by 17.5-23.2% after i.p. capsaicin (150-1,500?μg/kg), respectively. GSH decreased by 39.3-64.3% and by 35.7-41.1% after i.g. or i.p. capsaicin (150-1,500?μg/kg), respectively. Brain GSH increased significantly after the highest dose of i.g. or i.p. capsaicin (by 20.6 and 15.9%, respectively). The increase in serum ALT and ALP after endotoxin administration was decreased by oral or i.p. capsaicin. Serum nitric oxide showed marked increase after LPS injection, but was markedly decreased after capsaicin (1,500?μg/kg, i.p.). Serum glucose increased markedly after the administration of LPS, and was normalized by capsaicin treatment. It is suggested that in the presence of mild systemic inflammation, acute capsaicin administration might alter oxidative status in some tissues and exert an anti-inflammatory effect. Capsaicin exerted protective effects in the liver and lung against the LPS-induced tissue damage.     

溴莫普林片的人体药物动力学

目的测定国产溴莫普林(BDP)片在人体内的药物动力学.方法18名健康志愿受试者,单剂量po国产BDP片,用反相高效液相色谱法测定血浆中药物浓度.结果BDP药物动力学参数分别为cmax=(4.37±0.36)mg/L,tmax=(3.3±0.3)h,T1/2α=(5.54±6.24)h,T1/2β=(43.2±8.4)h,Cl=(1.84±0.27)L/h,Vd=(82.6±14.8)L,AUC0→∞=(198.89±26.91)h*mg/L.结论国产BDP片主要药物动力学参数与国外文献报道相似.     

Pharmacokinetics of oral pramiracetam in normal volunteers

The pharmacokinetics of pramiracetam, a new, investigational, cognition activator, were assessed in normal male volunteers as part of a clinical tolerance study. In a double-blind, randomized design, two groups of six subjects each received alternating placebo and single 400, 800, 1,200, and 1,600 mg oral doses of pramiracetam after an overnight fast. Mean (+/- SD) peak plasma concentrations of the four dose groups (2.71 +/- 0.54, 5.40 +/- 1.34, 6.13 +/- 0.71, 8.98 +/- 0.71 micrograms/mL) were attained between two to three hours following drug administration. The harmonic mean elimination half-life (4.5-6.5 hours), the mean total body clearance (4.45-4.85 mL/min/kg), the mean renal clearance (1.83-3.00 mL/min/kg), and the mean apparent volume of distribution (1.82-2.94 L/kg) were independent of dose, whereas the peak plasma concentrations and area under the curves increased as a linear function of dose. No significant side effects were observed at any dose level.     

Pharmacokinetics of propranolol in normal healthy volunteers

The pharmacokinetics of propranolol in blood was studied in healthy volunteers, following intravenous administration of 0.1 mg/kg and increasing oral doses of 10,20, and 40 mg, using a specific and sensitive gas Chromatographie method. The systemic availability of orally administered propranolol varied from 9% to 38% between subjects, but it was constant within each subject. A linear relationship was found between the area under the blood concentration-time curve and the oral dose. At variance with literature data, we could not observe a threshold dose.     

Reinforcing properties of lorazepam in normal volunteers

These experiments were designed to test the positive reinforcing property of a benzodiazepine in normal volunteer subjects. A choice procedure was used to measure preference for lorazepam, a benzodiazepine with a relatively short plasma half-life, over placebo. In separate experiments, subjects were given a choice between three doses of lorazepam (0.5, 1.0 and 2.0 mg, p.o.) and placebo, and in a fourth experiment subjects were given a choice between lorazepam (1.0 mg) and a therapeutically equipotent dose of diazepam (5 mg). Subjective effects of the drugs were monitored using an experimental version of the Profile of Mood States and a shortened version of the Addiction Research Center Inventory. Subjects showed no preference for 0.5 mg lorazepam over placebo (49% drug choice) or for 1.0 mg lorazepam over diazepam (46% lorazepam choice). However, subjects preferred placebo to both 1.0 and 2.0 mg lorazepam (32% and 16% drug choice for 1.0 and 2.0 mg, respectively). Subjective effects were consistent with the drug's known sedative and anxiolytic properties. Relative to diazepam, lorazepam had a longer duration of effect than might be expected from its plasma half-life. Differences in the pharmacokinetic properties of the two drugs account for the results. The results showed that lorazepam is not an effective positive reinforcer in these subjects, suggesting that it also does not have high dependence potential in this population.     

罗红霉素胶囊的人体生物等效性

目的:评价2种罗红霉素胶囊的生物等效性。方法:20名健康受试者单剂量随机交叉口服2种罗红霉素胶囊150 mg,采用HPLC-MS法测定血药浓度。结果:2种罗红霉素制剂的T1／2分别为(13.18±2.01),(13.31±2.45)h,tmax分别为(1.8±1.2),(2.2±1.1)h;cmax分别为(6.14±1.76),(6.47±2.42)nag·L-1,AUC0→72h分别为(71.81±28.40),(73.12±31.77)mg·h·L-1,受试制剂的相对生物利用度为(100.6±11.4)％。结论:2种制剂具有生物等效性。     

The neuropsychiatric effects of aspartame in normal volunteers

Ten healthy volunteers with no history of aspartame intolerance (6 men and 4 women, aged 21-36 years) received a single dose of aspartame (15 mg/kg body weight in capsules) or matching placebo in a randomized, double-blind crossover study. Eleven blood samples collected over 24 hours were analyzed for plasma glucose and amino acid concentrations. The following variables were evaluated at 1, 2, 4, 8, and 24 hours post-dosage: changes in mood measured on visual analog scales, cognitive function determined by digit-symbol substitution test (DSST) and arithmetic test scores, and reaction time measured with a brake-pedal reaction timer. Memory was tested at 2 and 24 hours after dosage based on recall of standardized 16-item word lists. No significant differences between aspartame and placebo were found in measures of sedation, hunger, headache, reaction-time, cognition, or memory at any time during the study. Plasma phenylalanine levels were significantly higher following aspartame (P less than .01) than with placebo between 1 and 6 hours postdosage, reaching a maximum difference of +3.36 mumols/dl at 2 hours. Plasma glucose concentrations were not significantly different between aspartame and placebo. The results of this study suggest that following a single 15 mg/kg dose of aspartame, no detectable effects are observed in a group of healthy volunteers with no history of aspartame intolerance, despite significant increases in plasma phenylalanine concentrations.     

Cognitive effects of lithium treatment in normal volunteers

Patients taking lithium often report difficulties in concentration, memory, learning, and attention and many of these complaints are verified on psychometric testing. Laboratory tests of cognitive functions in healthy volunteers on chronic lithium demonstrate that disruptions in memory-learning processes are apparent at the time of memory retrieval. Subjects, following chronic lithium treatment, produce more errors of commission in remembering previously occurring events while errors of omission appear to be unaffected. These effects are different from those produced by other psychoactive drugs that can also selectively alter and disrupt cognitive processes.     

国产克拉霉素胶囊人体生物利用度

目的:比较国产克拉霉素胶囊与进口克拉霉素片的人体生物利用度.方法:10名健康男性志愿者交叉单剂量po国产克拉霉素胶囊(A)和进口克拉霉素片(B).采用微生物法测定其血药浓度.计算药物动力学参数.结果:A、B两种剂型体内过程经药物动力学程序拟合,符合一空模型,C_(max)分别为(2.45±0.33)和(2.67±0.53)mg/L,t_(max)分别为(1.71±0.44)和(1.77±0.38)h,T(1/2)(ke)分别为(3.47±0.67)和(3.28±0.46)h,AUC分别为(16.84±3.19)和(17.68±2.25)[(mg/L)·h].经统计分析.两种制剂的药物动力学参数均无显著性差异(P>0.05).国产克拉霉素胶囊的相对生物利用度为95.16%.结论:两种制剂体内生物作用等效.