Abstract：
:Methodology used for the development of anti-Alzheimer's disease (AD) drugs raises specific problems which are rarely examined in the literature. While the general development scheme is similar to that required for most drugs, some specific aspects must be analyzed, highly dominated by the dual goal of pharmacology, i.e., to obtain both symptomatic and etiopathogenic drugs. During preclinical studies, aged or lesioned animals are mainly useful for symptomatic drugs, whereas transgenic models or neurodegeneration-induced techniques would probably lead to etiopathogenic drugs potentially slowing down the process of AD. The first administrations of a new compound to human beings raise the question of the activity measurement techniques. Psychometry remains the most informative procedure to detect and analyze the activity of the drugs on the different components of cognition. Electrophysiology and neuroimaging need some complementary studies before they can be proposed as surrogate criteria in phase III trials. At this stage of development, American and the recently published European guidelines are of great help while insisting on long-term (6 months) placebo controlled trials with the use of the triple efficacy criterion: an objective cognition scale, a global assessment, and the opinion of the caregiver. In the long term, pharmacoepidemiology and pharmacoeconomy will have to confirm the rationale of this recent progress in the methodology of anti-AD drug development.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Allain H,Bentué-Ferrer D,Zekri O,Schück S,Lebreton S,Reymann JMdoi
10.1111/j.1472-8206.1998.tb00919.xsubject
Has Abstractpub_date
1998-01-01 00:00:00pages
13-29issue
1eissn
0767-3981issn
1472-8206pii
S0767398198802235journal_volume
12pub_type
杂志文章,评审abstract：:Macrophage inflammatory protein (MIP)-1beta and RANTES (regulated on activation, normal T-cells expressed and secreted) are members of the CC-family of chemokines. Although these two peptides are structurally and functionally related to one another, each exhibits distinct features, which allows it to independently reg...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2003.00227.x
更新日期：2004-04-01 00:00:00
abstract：:The action of ouabain, a cell membrane Na+, K+-ATPase blocker, on contractions induced by manganese ions (Mn2+) in Ca2+-free, isotonic solutions with varying concentrations of K+ in the external medium were investigated in order to evaluate the underlying role of external Na+ in Mn2+-induced contractions in isolated t...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2005.00334.x
更新日期：2005-06-01 00:00:00
abstract：:Although nisoxetine has been shown to elicit cutaneous (peripheral) anesthesia, spinal (central) anesthesia with nisoxetine was not exposed. The aim of this study was to examine spinal anesthesia of nisoxetine and its influence on the antinociceptive action of mepivacaine. We compared nisoxetine with an established lo...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2012.01070.x
更新日期：2014-02-01 00:00:00
abstract：:We studied the effects of KATP channel blockers on [3H]GABA release in the absence of glucose in rat hippocampal slices. The omission of glucose induced a marked increase in the efflux of [3H]GABA, which was antagonized by TTX (1 microM), but not by MK 801 (1 microM) or DNQX (100 microM). Glibenclamide (10-100 microM)...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1992.tb00123.x
更新日期：1992-01-01 00:00:00
abstract：:Occlusion of the artery of organs results in ischaemia. The opening of occluded artery results in tissue lesion identified as reperfusion injury (RI). Renin-angiotensin system seems to be involved in the RI. In this study we assessed the effects of different doses of two inhibitors of angiotensin converting enzyme (ca...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1472-8206.2003.00188.x
更新日期：2003-10-01 00:00:00
abstract：:The hypothesis of an interaction between trimetazidine and the immunosuppressive effect of cyclosporin A was investigated in two models: a) ex vivo, the lymphoproliferative response of normal human lymphocytes to phytohemagglutinin and a murine monoclonal antibody against the CD3 T-lymphocyte membrane complex; b) in v...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1996.tb00305.x
更新日期：1996-01-01 00:00:00
abstract：:Strong sero-epidemiologic, pathologic, and experimental evidence suggests that Chlamydophila pneumoniae (Cpn) infection may play a causative role in the development of atherosclerosis. Cpn is an obligate intracellular gram-negative bacterium that is responsible for 10% of cases of community-acquired pneumonia. In addi...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1472-8206.2010.00863.x
更新日期：2010-10-01 00:00:00
abstract：:In the present study, we analysed the effects of leptin on rabbit aorta and the mechanisms underlying these effects. Leptin (10(-12)-10(-9) m) induced concentration-dependent relaxation in intact rabbit aorta rings precontracted with phenylephrine (10(-6) m). Removal of endothelium abolished the effects of leptin. Pre...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2007.00541.x
更新日期：2007-12-01 00:00:00
abstract：:The aim of our study was to analyse the protective effects of different alpha-tocopherol analogues 1) against fibrillations induced by an ischemia-reperfusion sequence, and 2) to further investigate in vitro the radical scavenging properties of these analogues by two sensitive methods. Concerning 1: isolated rat heart...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1998.tb00937.x
更新日期：1998-01-01 00:00:00
abstract：:Clinical research in chronic heart failure has recently focused on the stimulated neuro-hormonal compensatory mechanisms that could contribute to auto-aggravation of the disease. On the basis of such a hypothesis, and apart from the inhibition of the renin angiotensin system, the antagonism of beta-receptors has evolv...
journal_title：Fundamental & clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1997-01-01 00:00:00
abstract：:The effects of the dopamine receptor agonist, apomorphine, on the total catecholamine content of the adrenal medulla were studied in normotensive rats. Apomorphine (3, 15, 30 mg/kg SC) induced a dose-dependent decrease in catecholamine content of the adrenal gland. The action of apomorphine was suppressed by previous ...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1989.tb00467.x
更新日期：1989-01-01 00:00:00
abstract：:We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2004.00295.x
更新日期：2004-12-01 00:00:00
abstract：:By use of a simple anticonflict procedure (Vogel test), it was demonstrated that L-pyroglutamic acid (L-pyrrolidone carboxylic acid [L-PCA]), an amino acid naturally occurring in mammalian tissues and fluids, possesses anxiolytic activity. This tissues and fluids, possesses anxiolytic activity. This effect was stereos...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1988.tb00623.x
更新日期：1988-01-01 00:00:00
abstract：:Restenosis after coronary angioplasty, the main limitation of interventional cardiology, remains an unsolved issue. The failure to-date of all pharmacological attempts at prevention has prompted the development of alternative strategies. A mechanistic approach to the problem of restenosis is based on the assumption th...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1472-8206.1995.tb00259.x
更新日期：1995-01-01 00:00:00
abstract：:Isoniazid is the first-line treatment for tuberculosis; however, its use is limited by hepatotoxicity. Age-related differences in isoniazid pharmacokinetics and hepatotoxicity are uncertain. We aimed to investigate these in young (3 ± 0 months, n = 26) and old (23.0 ± 0.2 months, n = 27) male Fischer 344 rats followin...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/fcp.12157
更新日期：2016-02-01 00:00:00
abstract：:The aim of this study was to investigate biochemical and antioxidant parameters in alloxan-resistant (ALR) and alloxan-susceptible (ALS) rats. Diabetes was induced in 60-day-old male Wistar rats by a single intraperitonial injection of alloxan (AL, 150 mg/kg). Ten days after induction, a group of rats showed a signifi...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2008.00628.x
更新日期：2008-12-01 00:00:00
abstract：:Considering the diseases of the stomach and duodenum, peptic ulcer has been the one with a significant clinical impact. The pathophysiology of peptic ulcer has centred on an imbalance between aggressive and protective factors. The discovery of Helicobacter pylori as a cause of peptic ulcer has changed our approach gre...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1472-8206.2004.00203.x
更新日期：2004-02-01 00:00:00
abstract：:The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent s...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/fcp.12038
更新日期：2014-06-01 00:00:00
abstract：:Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclus...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1472-8206.2010.00865.x
更新日期：2011-08-01 00:00:00
abstract：:Allopurinol, oxypurinol, hypoxanthine and xanthine were assayed simultaneously using a highly specific method combining gas chromatography and mass spectrometry. Two hypo-uricaemic prescriptions were compared: i) 300 mg of allopurinol (AL); and ii) 100 mg of allopurinol plus 20 mg of benzbromarone (AL + BZB). When adm...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1991.tb00751.x
更新日期：1991-01-01 00:00:00
abstract：:Rhodamine 123 is a fluorescent cationic dye commonly used as a mitochondrial probe and known or suspected to be transported by certain drug membrane transporters. The present study was designed to characterize the putative interactions of rhodamine 123 with human organic cation transporter (OCT) 1 and OCT2. Intracellu...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2012.01071.x
更新日期：2014-02-01 00:00:00
abstract：:In France, prescription of narcotics must be written on a tamper-resistant prescription form with specific technical particularities. Dosage and daily dose of medicines shall be written out entirely in letters. These prescription forms are also mandatory for buprenorphine, clorazepate, clonazepam, tianeptine, buccal m...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/fcp.12368
更新日期：2018-10-01 00:00:00
abstract：:Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs for treating hypertension and congestive heart disease. It has been reported, however, that these drugs could induce chronic cough and airway hyperresponsiveness. The aim of this work was to assess in pigs the effects of bradykinin and tac...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1472-8206.2001.00008.x
更新日期：2001-02-01 00:00:00
abstract：:The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking t...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2006.00412.x
更新日期：2006-08-01 00:00:00
abstract：:Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) activities were detected in bronchial and bronchial epithelial cell homogenates of the pig. In the bronchial homogenates, the maximal upstroke velocity (Vmax) of AChE and the maximal velocity after second substrate fixation (Vss) of B...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1997.tb00186.x
更新日期：1997-01-01 00:00:00
abstract：:The aim of this study was to investigate which principal human cytochrome P450 (CYP450) enzymes are affected by artemisinin and to what degree the artemisinin derivatives differ with respect to their respective induction and inhibition capacity. Seventy-five healthy adults were randomized to receive therapeutic oral d...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1472-8206.2007.00471.x
更新日期：2007-06-01 00:00:00
abstract：:The present study investigated the effects of positive end-expiratory pressure (PEEP) on propofol concentrations in humans. Eleven patients undergoing elective surgery were enrolled in this study. Anesthesia was induced with propofol, then maintained using 60% nitrous oxide in oxygen, fentanyl 10-20 microg/kg and cont...
journal_title：Fundamental & clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1472-8206.2006.00436.x
更新日期：2006-10-01 00:00:00
abstract：:Endocannabinoid system has attracted the researchers to investigate into its ever fascinating roles governing many of the physiological functions in the human body. The prime endogenous cannabinoids are arachidonoylethanolamide also called anandamide and 2-arachidonoylglycerol. Recent pharmacological advances point ou...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1472-8206.2006.00454.x
更新日期：2007-02-01 00:00:00
abstract：:Drugs have side effects that manifest as signs or symptoms which are sometimes undistinguishable from signs or symptoms of active disease. The conventional approximation of the rate of side effects of drugs is by subtracting the rate of signs and symptoms in the placebo group from that in the drug group. This measures...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.1995.tb00537.x
更新日期：1995-01-01 00:00:00
abstract：:Two 5HT(1A) receptor agonists and chlordiazepoxide were examined in open-field, elevated plus maze, and emergence tests. At doses with no effect in the open-field, chlordiazepoxide increased open and open/total arm visits as well as open arm duration in the elevated plus maze, whereas 5HT(1A) receptor agonists showed ...
journal_title：Fundamental & clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1472-8206.2009.00772.x
更新日期：2010-06-01 00:00:00
