SEARCH · PubMed Health

Results for “efficacy”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1983

Post-operative dental pain and analgesic efficacy. Part II. Analgesic usage and efficacy after dental surgery.

The analgesics taken by patients after oral and periodontal surgery were noted over a three day observation period. Analgesic consumption matched closely the pain experience. The efficacy of self-prescribed analgesics was extrapolated from the pain scores obtained in the first 12 hours after surgery, and overall, the apparent efficacy appears poor. However, those patients who reported taking aspirin recorded significantly less pain than those who took either paracetamol or combination analgesics. Analgesic efficacy was not related to dose, although a significant correlation was noted between the number of paracetamol tablets taken and pain severity.

Adult↗

PubMed2006

Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial.

OBJECTIVES: The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine. BACKGROUND: Ranolazine is a unique antianginal agent that has been effective in stable angina, but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents. METHODS: Stable patients with coronary disease and > or =3 anginal attacks per week despite maximum recommended dosage of amlodipine (10 mg/day) were randomized to 1,000 mg ranolazine or placebo twice a day for 6 weeks. Primary end point was the frequency of angina episodes per week during the double-blind treatment phase. Efficacy was also assessed by nitroglycerin consumption per week and the Seattle Angina Questionnaire (SAQ). Adjustment for multiple testing of secondary end points used a hierarchic closed testing procedure. Efficacy was assessed in subgroups based on baseline angina frequency, concomitant long-acting nitrate use, gender, and age. Safety was assessed by adverse events and electrocardiogram evaluations. RESULTS: A total of 565 patients were randomized: 281 patients to ranolazine and 284 patients to placebo. Baseline characteristics were similar between treatment groups. At baseline, angina frequency averaged 5.63 +/- 0.18 episodes/week, and nitroglycerin consumption averaged 4.72 +/- 0.21 tablets/week. Compared with placebo, ranolazine significantly reduced frequency of angina episodes (2.88 +/- 0.19 on ranolazine vs. 3.31 +/- 0.22 on placebo; p = 0.028) and nitroglycerin consumption (2.03 +/- 0.20 on ranolazine vs. 2.68 +/- 0.22; p = 0.014), with treatment effect that appeared consistent across subgroups. The median angina weekly episode rate at baseline was 4.5 per week. Subgroup analysis showed statistically significant reductions of angina frequency, nitroglycerin use, and SAQ angina frequency for patients with a baseline frequency >4.5 per week but only of angina frequency for those with baseline frequency < or =4.5 per week. Patients with more frequent angina appeared to have a more pronounced treatment effect. No hemodynamic changes were observed. Ranolazine was well tolerated. CONCLUSIONS: Ranolazine significantly reduced frequency of angina and nitroglycerin consumption compared with placebo and was well tolerated. (The ERICA [Efficacy of Ranolazine In Chronic Angina] Trial; http://clinicaltrials.gov; NCT00091429).

Acetanilides↗

PubMed2000

Efficacy of intravenous citalopram compared with oral citalopram for severe depression. Safety and efficacy data from a double-blind, double-dummy trial.

BACKGROUND: Intravenous administration is often beneficial in the treatment of severely depressed patients. It is mainly the tri- and tetracyclic antidepressant drugs that can be administered intravenously. However, these drugs have a less favourable safety profile than newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). Citalopram is the only SSRI that is available in a formulation for infusion. This double-blind, randomised, multicentre trial was designed to compare the efficacy and tolerability of citalopram infusion (40 mg per day) and citalopram tablet (40 mg per day). METHODS: Patients were randomised to receive either placebo tablet plus citalopram infusion (the infusion group; n=135) or citalopram tablet plus placebo infusion (the tablet group; n=119). After receiving randomised treatment for eight days, all patients entered an open treatment phase, during which they received oral citalopram 40 mg per day for five weeks. RESULTS: Although there was no difference in Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of the randomised treatment period, by the end of the open treatment phase the reduction in MADRS scores was significantly greater in the infusion group than in the tablet group (p=0.015). The infusion group also showed superior efficacy in Clinical Global Impressions assessments. Citalopram was equally well tolerated in both treatment groups. CONCLUSIONS: This trial confirmed the efficacy of citalopram 40 mg per day, and clearly supports the use of citalopram infusion in the treatment of severely depressed, hospitalised patients.

Administration, Oral↗

PubMed2003

The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy.

INTRODUCTION: Atypical antipsychotics form a new class of treatment for psychotic disorders that offers advantages over conventional antipsychotics, such as haloperidol. Among these advantages is a lower risk of side effects-in particular movement disorders. The atypical antipsychotics that are currently commercially available are clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. The focus of this report is on the efficacy of quetiapine. DATA SOURCES/STUDY SELECTION: A meta-analysis was performed on three placebo- and five haloperidol-controlled clinical trials of quetiapine. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Scale for the Assessment of Negative Symptoms (SANS). In addition, a responder analysis was performed assessing patients who demonstrated a 40% improvement on the BPRS total score. RESULTS: The results showed that quetiapine was significantly (p<0.05) superior to placebo in improving psychotic symptoms. In addition, quetiapine was not significantly different from haloperidol on measures of efficacy measured by BPRS change score, but was superior to haloperidol in terms of response rate using observed case analysis (but not using last observation carried forward analysis). CONCLUSION: This meta-analysis supports the use of quetiapine as a front-line treatment for schizophrenia.

Antipsychotic Agents↗

PubMed1999

Novel potent and selective central 5-HT3 receptor ligands provided with different intrinsic efficacy. 2. Molecular basis of the intrinsic efficacy of arylpiperazine derivatives at the central 5-HT3 receptors.

Novel 5-HT3 receptor ligands were designed and synthesized with the aim of obtaining deeper insight into the molecular basis of the intrinsic efficacy of arylpiperazines interacting with the central 5-HT3 receptor. The newly synthesized compounds and some previously published compounds belonging to the same class of heteroarylpiperazines were tested for their potential ability to displace [3H]granisetron from rat cortical membranes. These 5-HT3 receptor binding studies revealed subnanomolar affinity in several of the compounds under study. The most active ligands were quipazine derivatives bearing a phenyl group in the 4-position and various oxygenated alkyl side chains in the 3-position of the quinoline nucleus. Qualitative and theoretical quantitative structure-affinity relationship studies were carried out, and the interaction model for the 5-HT3 ligands related to quipazine with their receptor, proposed in part 1 of the present work, was updated to incorporate the latest data. The potential 5-HT3 agonist/antagonist activity of 12 selected compounds was assessed in vitro on the 5-HT3 receptor-dependent [14C]guanidinium uptake in NG 108-15 cells. Their intrinsic efficacy ranged from the 5-HT3 full agonist properties of compounds 7a and 8h, i to those of partial agonists 10a,d and antagonists 8b,d,e, and 9c, d,h,i. The comparison between these functional data and those relative to the previously described compounds suggested that in this class of 5-HT3 ligands the intrinsic efficacy is modulated in a rather subtle manner by the steric features of the heteroaryl moiety.

Animals↗

PubMed2003

Quality, efficacy and safety of complementary medicines: fashions, facts and the future. Part II: Efficacy and safety.

This is the second of two papers which review issues concerning complementary medicines. The first reviewed the extent of use of complementary medicines, and issues related to the regulation and pharmaceutical quality of these products; the second considers evidence for the efficacy of several well-known complementary medicines, and discusses complementary-medicines pharmacovigilance. The term complementary medicines describes a range of pharmaceutical-type preparations, including herbal medicines, homoeopathic remedies, essential oils and dietary supplements, which mainly sit outside conventional medicine. The use of complementary medicines is a popular healthcare approach in the UK, and there are signs that the use of such products is continuing to increase. Patients and the public use complementary medicines for health maintenance, for the treatment or prevention of minor ailments, and also for serious, chronic illnesses. There is a growing body of evidence from randomized controlled trials and systematic reviews to support the efficacy of certain herbal extracts and dietary supplements in particular conditions. However, many other preparations remain untested. Strictly speaking, evidence of efficacy (and safety) for herbal medicines should be considered to be extract specific. Pharmacovigilance for complementary medicines is in its infancy. Data are lacking in several areas relevant to safety. Standard pharmacovigilance tools have additional limitations when applied to investigating safety concerns with complementary medicines.

Complementary Therapies↗

PubMed1995

How do physicians determine when to perform an "on-drug" electrophysiology study for efficacy determination in patients with sustained ventricular tachyarrhythmias: a previously unaddressed variable that may affect efficacy rates.

In patients with ventricular tachyarrhythmias, efficacy rates of antiarrhythmic agents, as judged by serial electrophysiological (EP) tests, have been variable. Factors underlying this variability have been reported to include: specific drug, type of arrhythmia, type of heart disease, left ventricular function, and number of prior drug failures. We hypothesized that variability in physician practice behavior as to when a drug assessment is performed might be another important factor affecting drug efficacy. Using a survey sent to 103 electrophysiology centers we determined from the 46 respondents that this is indeed the case. Twenty-six of the 46 respondents always, 9 of 46 sometimes, and 11 of 46 did not require ectopy reduction on continuous electrocardiographic monitoring before proceeding to an EP study. The ectopy reduction required, however, varies among physicians in percentage and type. Twenty-seven of the 35 respondents who utilize rhythm monitoring also require attainment of an acceptable blood level, a prespecified minimal target dose, and/or one or more ECG interval changes prior to proceeding to EP testing. Fifteen out of 46 do not require "therapeutic" drug levels. Of 11 who don't use rhythm monitoring, 5 also don't use blood levels. The lower value for "therapeutic ranges" varied by up to 3-fold and the upper value by up to 2 1/2-fold for individual drugs. The minimum time for testing varied from 1 half-life to over 10 half-lives. Similarly, the response to failure of a submaximal dose also varied: 9% always retested at a high dose, 2% never tested at a higher dose, and 91% were inconsistent. Moreover, what was considered the maximal dose for an individual drug varied by 3- to 6-fold for most agents queried. We believe these variations in dose, time, and coassessment factors must have an influence on efficacy rates of antiarrhythmic agents.

Anti-Arrhythmia Agents↗

PubMed1993

Methods of projecting long-term relative efficacy of products exhibiting small short-term efficacy.

There is ample evidence that caries can develop well into the middle-aged years, and for many subjects, for most of their adult lives. The kinds of benefits to expect for adults in the longer term for improved fluoride products, especially dentifrices, based upon small observed relative improvements in short-term efficacy is a topic currently of considerable interest. For example, what longer-term benefits can be expected by the continued use of an improved fluoride dentifrice, corresponding to an observed 5% or 10% short-term improved efficacy relative to a positive control product? In this study, three models are presented and discussed for projecting longer-term relative benefits of fluoride products for which valid short-term efficacy estimates are available: the compound growth model (CGM), which is a derivative of the compound interest model; the demineralization square root model (DSR), used in demineralization-remineralization studies, and the stabilization model (STA), which is based on the assumption of constant caries attack rates. Published results from long-term studies of fluoride dentifrices and other topical fluoride products (rinses and tablets) suggest that anticaries benefits for topical fluorides do propagate over time, providing increased relative benefits to patients in the longer-term, as compared with the benefit estimates from short-term clinical experiences.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

PubMed2000

A study to evaluate the field efficacy of ivermectin, fenbendazole and pyrantel pamoate, with preliminary observations on the efficacy of doramectin, as anthelmintics in horses.

The efficacy of ivermectin, fenbendazole, pyrantel pamoate and doramectin was evaluated under field conditions at 2 sites in the Free State Province of South Africa. The study involved 25 horses at each site, divided into 5 groups of equal size. Ivermectin, fenbendazole and pyrantel pamoate were administered orally at doses of 0.2, 10 and 19 mg/kg respectively. Doramectin was administered by intramuscular injection at a dose of 0.2 mg/kg. Treatment efficacy was based on the mean faecal egg count reduction 14 days post treatment. At site A a faecal egg count reduction of 100% was found after treatment with ivermectin, fenbendazole and doramectin. A 96.1% reduction was found after treatment with pyrantel pamoate. At site B ivermectin and doramectin produced a 100% reduction in faecal egg counts, fenbendazole produced an 80.8% reduction and pyrantel pamoate a 94.1% reduction. Doramectin produced a 100% reduction in faecal egg counts at both sites, despite not being registered for use in horses. In addition, the results indicated reduced efficacy of fenbendazole at site B, which suggested benzimidazole resistance. Larval cultures showed that cyathostomes accounted for between 86 and 96% of pre-treatment parasite burdens at both sites. Other helminths identified in the faecal samples were Strongylus spp. and Trichostrongylus axei.

Animals↗

PubMed2004

Comparative efficacy of wheal-and-flare suppression among various non-sedating antihistamines and the pharmacologic insights to their efficacy.

BACKGROUND AND OBJECTIVE: Non-sedating antihistamines (loratadine, fexofenadine, and cetirizine) have been widely used in Thailand. This study examined the time-of-onset and compared the 95% inhibitory effect of these agents on histamine-induced cutaneous reaction so as to understand the diversity of their efficacy. PATIENTS AND METHOD: Thirty-one atopic patients were randomized into 4 treatment groups, placebo (n = 7), loratadine (n = 8), fexofenadine (n = 8), and cetirizine (n = 8). They were pricked with histamine every 30 min for 4 hrs. The percentage change of the wheal/flare area was calculated. RESULTS: All active treatments showed wheal suppression superior to placebo after 210 min for loratadine (P = 0.04); 90 min for fexofenadine (P = 0.009); and 60 min for cetirizine (P = 0.02), while flare suppression was significantly marked after 150 min (P = 0.0008) for loratadine; 90 min for fexofenadine (P = 0.0001), and 60 min for cetirizine (P = 0.006). All drugs except loratadine demonstrated a 95% suppression of wheal superior to the placebo (P = 0.001 for fexofenadine; P = 0.0001 for cetirizine). Only fexofenadine exhibited a 95% suppression of flare statistically superior to placebo (P = 0.02). Discrepancies among the effects of these 3 antihistamines were also detected. DISCUSSION AND CONCLUSION: All antihistamines tested repressed the wheal-and-flare area superbly over the placebo within 4 hours. Cetirizine exerted the fastest onset, and it also appeared to be the most efficacious inhibitor. The heterogeneity of their efficacy probably stems from their diverse physicochemical properties, which have also been discussed.

Adolescent↗

PubMed1974

Factors affecting the efficacy of live poliovirus vaccine in warm climates. Efficacy of type 1 Sabin vaccine administered together with antihuman gamma-globulin horse serum to breast-fed and artificially fed infants in Uganda.

A virologically controlled field trial was conducted with live monovalent type 1 poliovirus vaccine in children aged 3-30 months living in a rural area of Uganda, in an attempt to find out the reason for the poor efficacy of such vaccine often observed in countries with a warm climate. Groups of breast-fed and of artificially fed infants received the vaccine orally, either alone or mixed with horse serum prepared against partly purified human gamma-globulin. Irrespective of the diet, the "take rate"-measured by the rates of vaccine virus excretion and of antibody conversion-was found to be poor when the vaccine was given alone but satisfactory when it was given together with the horse antiserum. However, the extent and duration of vaccine virus multiplication in the intestinal tract proved to be limited and the mean antibody level elicited by the vaccination, irrespective of the schedule of vaccine administration, was low. These results, besides indicating that breast-feeding does not influence the efficacy of vaccination in the age groups studied, revealed the presence of an inhibitor in the alimentary tract. This inhibitor acts against the multiplication of vaccine virus, which may be blocked by antibodies in the horse antiserum for a limited period at the time of vaccination. Interference between the enteroviruses and the vaccine strain was also found to be responsible for decreasing the efficacy of vaccination, though its role was secondary to that of the inhibitor. Revaccination experiments showed that the effects of both inhibitor and interference may be overcome by repeated administration of the vaccine.

Breast Feeding↗

PubMed1993

Critique of Kingman's methods of projecting long-term relative efficacy of products exhibiting small short-term efficacy.

This paper critically reviews Kingman's "methods of projecting long-term relative efficacy of products exhibiting small short-term efficacy," a report he prepared for a scientific workshop on the relative anticaries efficacy of fluoride dentifrices, which reveals serious deficiencies. Of the three specific models that Kingman suggests, the compound growth model (CGM), which leads to the largest projected future percentage reductions, is based on a false premise of an increasing universe of caries-free surfaces available for caries-attack with the passage of time. The second suggested model, the demineralization square root model (DSR), is supported only by a personal communication, unavailable for scrutiny. The third suggested model, a stabilization model (STA) is plausible, but unsupported. Other plausible models for extrapolating short-term observed effects are ignored by Kingman. Most of Kingman's choices of data illustrations to fit his suggested models are ill-chosen because the studies were repeated cross-sectional surveys or involved the delivery of systemically and topically delivered fluorides, which contraindicate their use. The most serious breach is Kingman's selective use of subsets of data from two long-term studies of fluoride dentifrices that support his premise, when other, more comprehensive data from the same studies do not. He also ignores findings from other studies that fail to support his suggested models. Kingman's report fails to prove that studies which show small short-term effectiveness after 1, 2 or 3 years will lead to greater relative effectiveness after long periods of use.

Cariostatic Agents↗

PubMed1996

Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.

OBJECTIVE: To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride. DESIGN: Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study. SETTING: Outpatient care in 28 centres across Canada. PARTICIPANTS: Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment. INTERVENTION: After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years. OUTCOME MEASURES EFFICACY: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. SAFETY: onset, course and resolution of all adverse events during the treatment period. RESULTS: In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters). CONCLUSION: Finasteride is a well-tolerated and effective alternative to watchful waiting in the treatment of moderate BPH.

Aged↗

PubMed1999

Efficacy of sustained blood levels of interleukin-1 receptor antagonist in animal models of arthritis: comparison of efficacy in animal models with human clinical data.

OBJECTIVE: To determine the role of interleukin-1 receptor antagonist (IL-1Ra) in rat adjuvant arthritis and rat type II collagen-induced arthritis, and to compare the efficacy in rat models with that seen in human clinical trials of IL-1Ra. METHODS: Rats with developing adjuvant arthritis or established collagen-induced arthritis were treated with IL-1Ra by continuous infusion in order to determine and maintain efficacious blood levels of this IL-1 inhibitory protein in the rats for comparison with human clinical data. The effects of treatment in the rats were monitored by sequential caliper measurement of the ankle joints, determination of final paw weights, and histologic evaluation with particular emphasis on bone and cartilage lesions. The effects of IL-1Ra on joint swelling and radiographic bone damage in patients with rheumatoid arthritis (RA) in a 6-month trial were compared with the findings in rats. RESULTS: Dramatic differences in the profile of IL-1Ra activity were seen between the 2 groups of rats. Modest antiinflammatory effects were observed in the adjuvant arthritis rats treated with IL-1Ra. However, marked inhibition of bone resorption occurred, even at doses with which antiinflammatory activity was not seen. In contrast, IL-1Ra treatment of rats with established collagen-induced arthritis resulted in nearly complete suppression of all aspects of the disease when adequate blood levels of IL-1Ra were maintained. Treatment of RA patients with IL-1Ra (150 mg daily) resulted in modest inhibition of joint swelling and inhibition of radiographic progression of bone lesions. CONCLUSION: IL-1 appears to be of major importance in mediating the bone resorption that occurs in rat adjuvant arthritis, but is less important in the pathogenesis of periarticular inflammation in this disease. In contrast, IL-1 is of major importance in mediating all aspects of disease progression in rat collagen-induced arthritis. Similar to the response in adjuvant arthritic rats, RA patients treated with IL-1Ra showed only modest antiinflammatory activity, but had evidence of inhibition of progression of bone resorption. However, a comparison of the plasma levels of IL-1Ra in humans and rats suggests that the optimal level of dosing for continuous saturation of IL-1 receptors may not have been achieved in humans, although this was achieved in the rat studies.

Animals↗

PubMed2005

Comparative study of the efficacy of eprinomectin versus ivermectin, and field efficacy of eprinomectin only, for the treatment of chorioptic mange in alpacas.

The efficacy of eprinomectin versus ivermectin (Study 1: a single-centre, randomised, treatment-controlled, blinded field trial), and the field efficacy of eprinomectin (Study 2: a single-centre, open, un-controlled field trial) for the treatment of chorioptic infestation in naturally infested alpacas were assessed in two studies. Thirty alpacas, all positive for Chorioptes sp. mite, were randomly allocated to two treatment groups in Study 1. Group A received a single topical administration of a 0.5% formulation of eprinomectin at the dose rate of 500mug/kg. Group B received three subcutaneous administrations at 14 days interval of a 1% formulation of ivermectin at the dose rate of 400mug/kg. Response to treatment was assessed by periodic mite count, and skin lesions scored. In Study 2, one group of 19 alpacas received four administrations at weekly interval of topical eprinomectin at the dose rate of 500mug/kg, and response to treatment was monitored by mite counts. No localised or systemic side effects were observed in either trial. There was a statistically significant decrease in mite counts on day 7 (P<0.001) within treatment Groups A and B of Study 1, but mite counts increased again on day 14 and remained high for the duration of the trial in both treatment groups. On day 14 of Study 2, there was a statistically significant reduction in mite counts (P<0.008) and the mite counts remained very low throughout the remainder of the study. The eprinomectin protocol employed in Study 2, consisting of four weekly topical administrations at the dose rate of 500mug/kg of body weight, proved highly effective at reducing the Chorioptes mite burden in alpacas.

Administration, Cutaneous↗

PubMed2001

Efficacy of antipsychotic agents at human 5-HT(1A) receptors determined by [3H]WAY100,635 binding affinity ratios: relationship to efficacy for G-protein activation.

5-HT(1A) receptors are implicated in the aetiology of schizophrenia. Herein, the influence of 15 antipsychotics on the binding of the selective 'neutral' antagonist, [3H]WAY100,635 ([3H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)-cyclo-hexanecarboxamide), was examined at human 5-HT(1A) receptors expressed in Chinese Hamster Ovary cells. In competition binding experiments, 5-HT displayed biphasic isotherms which were shifted to the right in the presence of the G-protein uncoupling agent, GTPgammaS (100 microM). In analogy, the isotherms of ziprasidone, quetiapine and S16924 (((R-2-[1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yloxy)-ethyl]-pyrrolidin-3yl]-1-(4-fluoro-phenyl)-ethanone), were displaced to the right by GTPgammaS, consistent with agonist actions. Binding of several other antipsychotics, such as ocaperidone, olanzapine and risperidone, was little influenced by GTPgammaS. Isotherms of the neuroleptics, haloperidol, chlorpromazine and thioridazine were shifted to the left in the presence of GTPgammaS, suggesting inverse agonist properties. For most ligands, the magnitude of affinity changes induced by GTPgammaS (alteration in pK(i) values) correlated well with their previously determined efficacies in [35S]GTPgammaS binding studies [Eur. J. Pharmacol. 355 (1998) 245]. In contrast, the affinity of the 'atypical' antipsychotic agent, clozapine, which is a known partial agonist at 5-HT(1A) receptors, was less influenced by GTPgammaS. When the ratio of high-/low-affinity values was plotted against efficacy, hyperbolic isotherms were obtained, consistent with a modified ternary complex model which assumes that receptors can adopt active conformations in the absence of agonist. In conclusion, modulation of [3H]-WAY100,635 binding by GTPgammaS differentiated agonist vs. inverse agonist properties of antipsychotics at 5-HT(1A) receptors. These may contribute to differing profiles of antipsychotic activity.

Animals↗

PubMed1996

Redistribution of synaptic efficacy: a mechanism to generate infinite synaptic input diversity from a homogeneous population of neurons without changing absolute synaptic efficacies.

Changing the reliability of neurotransmitter release results in a change in the efficacy of low frequency synaptic transmission and in the rate of high frequency synaptic depression thus it can not cause an uniform change in strength of synapses and instead results in a change in the dynamics of synaptic transmission referred to as 'redistribution of synaptic efficacy' (RSE). Since the change in synaptic transmission associated with RSE depends on the history of action potential activity it is concluded that RSE serves as a mechanism to generate a potentially infinite diversity of synaptic input.

Action Potentials↗

PubMed1999

Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing genotoxic effects produced by arsenic trioxide in mice: II. Comparative efficacy of an antibiotic, actinomycin D alone and in combination with either of two microdoses.

OBJECTIVE: To determine whether actinomycin-D (AMD), an antibiotic, alters the reported efficacy of a potentized homoeopathic drug, Arsenicum Album, in reducing genotoxic effects produced in arsenic-trioxide-injected mice. DESIGN: Mice were separately injected with AMD, As2O3, and conjointly with AMD plus As2O3, AMD plus homoeopathic drug, AMD plus As2O3 plus homoepathic drug, and As2O3 plus homoeopathic drug in separate sets. METHODS: Several standard cytogenetical endpoints were assessed at different fixation intervals by adopting conventional techniques. RESULTS: Both Ars Alb-30 and Ars Alb-200 showed protective ability against AMD and As2O3 when injected individually, but this ability was reduced considerably in mice injected with AMD and As2O3 together. AMD itself had genotoxic effects, but also apparently reduced genotoxic effects of arsenic to some extent. CONCLUSION: AMD reduced the protective efficacy of the homoeopathic drug against arsenic. This result suggests a mechanism of action for homoeopathy, as AMD is a known transcription-blocker.

Animals↗