ISRN Pharmacology最新文献

In vivo microdialysis was used in this study to reveal the role of cannabinoids in regulating serotonin (5-HT) efflux in the nucleus accumbens (NAcc) and dorsal raphe nucleus (DRN). The cannabinoid CB1 receptor agonists WIN55212-2 and CP55940 systematically administered to rats caused significant increases in 5-HT efflux in the NAcc but failed to have an effect in the DRN. To reveal mechanisms underlying regionally selective responses, we tested the hypothesis that cannabinoids have both direct and indirect effects on 5-HT efflux, depending on the location of CB1 receptors in the neural circuit between DRN and NAcc. We showed that the direct effect of cannabinoids caused a reduction in 5-HT efflux whereas the indirect effect resulted in an increase. Furthermore, the indirect effect was blocked by the GABA(A) receptor antagonist bicuculline in the DRN, suggesting that the action is likely due to a presynaptic inhibition on GABAergic activity that exerts a tonic influence on neuronal circuits regulating 5-HT efflux. Involvement of GABAergic neurons was confirmed by measuring changes in GABA efflux. Taken together, our study suggests that cannabinoids may have direct and indirect effects on the 5-HT regulatory circuits, resulting in regionally selective changes of 5-HT efflux in the brain.

Herbs and herbal products are considered to be safer and people mix it often with the oral hypoglycemic agent in diabetes therapy. But numerous reports say that every combination of herbs and drugs is not safe. Some combinations may be beneficial and some may be harmful also. So before taking any herbal remedies with oral hypoglycemic agent, patient should consult physician. In this paper we are summarizing the reports available on the interaction of herbal remedies to one of the oral hypoglycemic agents (glibenclamide) and categorizing the effect of the combination is beneficial and harmful.

The basic treatment goals of pharmacological therapies in sleep medicine are to improve waking function by either improving sleep or by increasing energy during wakefulness. Stimulants to improve waking function include amphetamine derivatives, modafinil, and caffeine. Sleep aids encompass several classes, from benzodiazepine hypnotics to over-the-counter antihistamines. Other medications used in sleep medicine include those initially used in other disorders, such as epilepsy, Parkinson's disease, and psychiatric disorders. As these medications are prescribed or encountered by providers in diverse fields of medicine, it is important to recognize the distribution of adverse effects, drug interaction profiles, metabolism, and cytochrome substrate activity. In this paper, we review the pharmacological armamentarium in the field of sleep medicine to provide a framework for risk-benefit considerations in clinical practice.

Context. Many diseases are associated with oxidative stress caused by free radicals. Objective. The present study evaluated the in vitro antioxidant and antibacterial activities of various extracts of aerial parts of Periploca aphylla and Ricinus communis. Materials and Methods. In vitro antioxidant activities of the plant extract were determined by DPPH and NO scavenging method. Superoxide anion radical activity was measured by the reduction of nitro blue tetrazolium as compared with standard antioxidants. Total phenolic contents and antibacterial activities of these plants were determined by gallic acid equivalent (GAE) and serial tube dilution method, respectively. Results. Plants showed significant radical scavenging activity. The results were expressed as IC(50). n-Propyl gallate and 3-t-butyl-4-hydroxyanisole were used as standards for antioxidant assay. All the extracts of both plants showed comparable IC(50) to those of standards. Plants extract exhibited high phenolic contents and antibacterial activities were comparable with standard drug, Ciprofloxacin. Discussion and Conclusion. The present study provides evidence that Periploca aphylla and Ricinus communis prove to be potent natural antioxidants and could replace synthetic antioxidants. Plants can also be used against pathogenic bacterial strains.

Cardiovascular complications and associated conditions remain a major cause of death, globally. Piliostigma thonningii has been used for different and several medicinal purposes. On this background, the effect of aqueous leaf extract of the plant on the lipid profile of physiologically normal rats was examined. Graded doses of the extract, 0.0, 0.2, and 0.4 g/kg of body weight (bwt) were orally administered to rats for a period of 14 days. The effect of the extract was assessed on the basis of comparative determinations of the evaluated indices in treated rats vis-à-vis the nontreated group as well as in respect to the differences between the basal and final concentrations of the indices in each group. The extract, especially at 0.2 g per kg body weight caused a significant decrease in the total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol in the treated rats when compared to the control group and basal concentrations. Though, the level of high-density lipoprotein (HDL) cholesterol increased in the treated rats, the increase was not significant when compared to the basal concentration. The LDL/HDL ratio in all the experimental groups was less than 0.9. The results obtained in this study suggest that P. thonningii aqueous leaf extract likely contains antilipidaemic and anticholesterolaemic substance(s), which may be useful in the prophylactic and curative management of lipid peroxidation, high blood pressure, and cardiovascular disorders.

The aim of the present study was to explore the hedonic effects of D(2) receptor agonist, quinpirole and D(2) receptor antagonist, and sulpiride alone or in combination with a low dose of 17β-E(2)-estradiol (17β-E(2)) in the adult ovariectomized female rats (OVX). OVX rats of Wistar strain were used in all experiments. Two weeks after surgery rats were chronically treated with vehicle, a low dose of 17β-E(2) (5.0 μg/rat), quinpirole (0.1 mg/kg), sulpiride (10.0 mg/kg), quinpirole plus 17β-E(2), or sulpiride plus 17β-E(2) for 14 days before the forced swimming test. We found that sulpiride significantly decreased immobility time in the OVX females. A combination of sulpiride with a low dose of 17β-E(2) induced more profound decrease of immobility time in the OVX rats compared to the rats treated with sulpiride alone. On the contrary, quinpirole failed to modify depression-like behavior in the OVX rats. In addition, quinpirole significantly blocked the antidepressant-like effect of 17β-E(2) in OVX rats. Thus, the D(2) receptor antagonist sulpiride alone or in combination with a low dose of 17β-E(2) exerted antidepressant-like effect in OVX female rats, while the D(2) receptor agonist quinpirole produced depressant-like profile on OVX rats.

Introduction. Sign and symptoms of rheumatoid arthritis have circadian rhythms and are more prominent in the morning. Timing of glucocorticoid administration may be important with respect to the natural secretion of endogenous glucocorticoids. Herein, we intended to test the hypothesis that bedtime administration of prednisolone could be more efficient in controlling signs and symptoms in patients with RA. Material and Methods. Sixty patients with stable disease were treated with single dose prednisolone at 8 a.m. for the first three months and thereafter with similar dose at 10 PM for the next three months (before-after method). We compared fatigue scores, morning stiffness and pain scores, Clinical Disease Activity Indices, erythrocyte sedimentation rates, C Reactive Protein, and profile of adverse effects. Results. The mean of morning stiffness, fatigue scores, CRP and CDAI decreased statistically when prednisolone was administrated at 10 p.m. The means of pain scores and ESR were also decreased when the patients took prednisolone at night, without significant statistical difference. Conclusion. Administration of low-dose oral prednisolone could reduce disease activity scores in morning in clinically stable patients with RA. So it could be supposed that administrating bedtime prednisolone may permit the smallest possible dose.

The present study was aimed to evaluate the protective effect of hesperidin against immobilization-stress-induced alterations in biochemical, behavioral, and mitochondrial functions in mice. In many instances neuroscientists have reported that acute immobilization stress for 6 h resulted in anxiety and impaired locomotor activity due to excess oxidative-nitrergic stress, depletion of antioxidant defense mechanisms, and mitochondrial dysfunction in animals. In the present study, 6 h of acute immobilization stress had significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in Swiss albino mice. Fourteen days of pretreatment with Hesperidin (50 and 100 mg/kg, p.o.) significantly and dose-dependently inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress. Furthermore, pre-treatment of l-arginine (50 mg/kg, i.p.), a nitric oxide precursor, reversed the protective effect of Hesperidin (50 and 100 mg/kg) (P < 0.05). In contrast, pretreatment of l-NAME (5 mg/kg, i.p.), a nitric oxide synthase inhibitor, potentiated the protective effect of Hesperidin (P < 0.05). These results suggest the possible involvement of nitrergic pathway in the protective effect Hesperidin against immobilization-stress-induced behavioral, biochemical, and mitochondrial dysfunction in mice.

The objective of this study was to investigate the bioequivalence of two formulations of 5 mg donepezil HCL tablets: Tonizep as the test and Aricept as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 3-week washout period in 20 healthy Thai Male volunteers. After drug administration, serial blood samples were collected over a period of 216 hours. Plasma donepezil concentrations were measured by high performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC(0-∞) and C(max) were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC(0-∞) and C(max) values of the test product over those of the reference product were 1.08 (1.02-1.14) and 1.08 (0.99-1.17), respectively (within the bioequivalence range of 0.8-1.25). The median T(max) for the test product was similar to that of the reference product (2.0 hr), and the 90% CI for the T(max) difference between the two preparations was -0.19 to 0.29 hr and within the bioequivalence range of ± 20% of the T(max) of the reference formulation. Our study demonstrated the bioequivalence of the two preparations.

The development of pharmacodynamic (PD) biomarkers in oncology has implications for design of clinical protocols from preclinical data and for predicting clinical outcomes from early clinical data. Two classes of biomarkers have received particular attention. Phosphoproteins in biopsy samples are markers of inhibition of signalling pathways, target sites for many novel agents. Biomarkers of apoptosis in plasma can measure tumour cell killing by drugs in phase I clinical trials. The predictive power of PD biomarkers is enhanced by data modelling. With pharmacokinetic models, PD models form PK/PD models that predict the time course both of drug concentration and drug effects. If biomarkers of drug toxicity are also measured, the models can predict drug selectivity as well as efficacy. PK/PD models, in conjunction with disease models, make possible virtual clinical trials, in which multiple trial designs are assessed in silico, so the optimal trial design can be selected for experimental evaluation.