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Traitements d'aujourd'hui et de demain 25/09/08
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alors, contactez-moi, merci. : delacourte*lille.inserm.fr
73,745 (MDL 73,745) Hoechst Marion Roussel Inc. Phase I (Trimethylsilylated trifluoromethyl ketones, a class of acetylcholinesterase inhibitors)
ABT-089
Sponsored by Abbott Laboratories Purpose
The purpose of this study is to compare the safety and efficacy of 2 mg, 4 mg,
and 20 mg of ABT-089 BID to placebo in adults with Alzheimer's disease.
Condition Treatment or Intervention PhaseAlzheimer's Disease Drug: ABT-089
Phase II
AF102B (cevimeline) Snow Brand Milk Products Co. M1 agonist Phase. III clinical
AIT-082 (NeoTherapeutics Inc, Phase II ) It can cross the blood-brain barrier and enhance nerve cell function by increasing levels of neurotrophic factors.
Purine derivative. Named "Neotrophin". http://www.clinicalstudies.net/releases/neothera.html ><http://www.pslgroup.com/dg/3362e.htm
ALCAR (acetyl-carnitine) Sigma-Tau Phase III
alpha-tocopherol, an anti-oxidant
Alzene Ivax. Corp. Phase II
Alzhemed: En phase III (3-APS, glycoaminoglycanne (cad un sucre complexe) qui neutraliserait la neurotoxicité de l'amyloïde))
Amiridin . Nikken Chemical Co AChE inhibitor Phase III clinical
Ampalex Cortex Pharmacueticals Inc Phase I
Memory deficiency Researchers would like to see if giving patients a drug that attaches to AMPA receptors improves the symptoms of Alzheimer's disease. CX516 (Ampalex) is a test drug that affects the AMPA receptors. This study will investigate the effectiveness and safety of CX516 on patients with Alzheimer's disease.
Amyloid protease inhibitors Cephalon, Inc Preclinical
Anti-inflammatories Anti-inflammatoires.
Apomorphine HCl Pentech Pharmaceuticals Phase II
Aricept (E-2020) (DONEPEZIL) Eisai Co Ltd. Acetylcholine inhibitor.Phase III finished. Commercialized. Molecular mechanism
AXURA http://www.merz.com/ http://www.memantine.com see Memantine
BC-PS (phosphatidylserine) Fidia Pharmaceutical Phase II
Besipiridine HCl (HP 749) Hoechst-Roussel Phase II/III
cevimeline (AF-102B) Snow Brand Milk Products M1 agonist Phase III
Cholinesterase inhibitor Marion Merrell Dow Phase II
Citalopram
The study is for people with Alzheimer's disease who are having trouble with their thinking or behavior. In particular, this study is trying to find out the best treatment for people who have hallucinations (seeing or hearing things that aren't there), delusions (false beliefs), or agitation
Clioquinol (CQ) Molécule qui complexe le cuivre associé à l'amyloide. Essai thérapeutique de phased II arrêté. Sera remplacé par un essai sur une molécule plus puissante: le PBT2
A) Cognex (tacrine) Acetylcholine inhibitor. Warner-Lambert . Commercialized for hospitals
B) Cognex. The point of view of Parke-Davis Molecular mechanism
The COGNIShunt® System
This is a study of the effect on the progression of Alzheimer's Disease of
a surgically implanted shunt (tube) to increase the flow of cerebrospinal fluid
and improve the clearance of potential neurotoxins from the fluid bathing the
brain.
Condition Treatment or Intervention Phase
Alzheimer Disease Device: Phase III
CX516 CX516 (Ampalex) is a test drug that affects the AMPA receptors. This study will investigate the effectiveness and safety of CX516 on patients with Alzheimer's disease. Phase II
D-CYCLOSERINE
The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled
clinical trials with statistical power high enough to detect a clinically meaningful
effect means that D-cycloserine has no place in the treatment of patients with
Alzheimer's disease.
Citation: Laake K, Oeksengaard AR. D-cycloserine for Alzheimer's disease (Cochrane
Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.
DAD 2000. " Dapsone in
Alzheimer Disease 2000" (DAD2000) Phase II clinical trial.
Company Contact: Rupinder Bagri, Corporate Communications
Immune Network Ltd. 3650 Wesbrook Mall, Vancouver, BC, Canada V6S
2L2
DAPSONE is in Phase 2 clinical trials for Alzheimer disease. Old drugs with new uses are ALWAYS very difficult to find, no matter how effective the drugs are.
DHEA.
Neuroscience Pharma Inc. Neurosteroid. Phase III clinical See Beaulieu and Forette,
The data offer no support at present for an improvement in memory or other
aspects of cognitive function following DHEA treatment in normal older people.In
view of the growing public enthusiasm for DHEA supplementation, particularly
in the USA, and the possibility that any neuroprotective effect of DHEA/S may
only be evident in the long term, there is a need to undertake high quality
trials in which the duration of DHEA treatment is longer than one year, and
the number of participants is large enough to detect effects if they exist.
Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal
women (USA), normal older men (UK), and a one-year trial in normal older men
and women (France) have been completed. As soon as the results are available
these studies will be included in the review.
Citation: Huppert FA, Van Niekerk JK. Dehydroepiandrosterone (DHEA) supplementation
for cognitive function. (Cochrane Review). In: The Cochrane Library, Issue 3,
2003. Oxford: Update Software.
Donepezil (E2020) (Aricept). Acetylcholine inhibitor. Eisai. Commercialized
Donepezil on an other site ...........About Eisai Molecular mechanism
E-2020 (see Aricept or Donepazil). Acetylcholine inhibitor. Eisai Molecular mechanism
Eldepryl (Selegiline), an anti-oxidant
ENS-163 Sandoz Phase I
ENA-713 (Exelon) Novartis Phase III. Sandoz. ....Acetylcholine inhibitor. Commercialized Molecular mechanism
Eptastigmine (MF-201) Mediolanum Pharmaceuticals Phase III
Estrogens : Could
be a neuroprotector, but therapeutic trials are not that good.
Study to examine whether the administration of estrogen to post-menopausal
women and women with mild to moderate Alzheimer's disease will enhance their
memory and their capacity for learning.
--------
Raloxifene, an estrogen-like medication approved by the Food and Drug Administration
for the treatment of osteoporosis, in improving memory and the ability to live
independently in postmenopausal women with Alzheimer's disease.
Condition Treatment or Intervention Phase
Alzheimer Disease Drug: Raloxifene Phase II
Phase III
------------------
This is a 15-month study to determine the effectiveness of hormone replacement
therapy in improving memory and the ability to live independently in postmenopausal
women with Alzheimer's disease.
Condition Treatment or Intervention Phase
Alzheimer Disease Drug: Transdermal 17-ß-estradiol
Drug: Medroxyprogesterone Phase II , Phase III
Des espoirs, mais non confirmés actuellement.
Exelon (ENA-713, Rivastigmine) Acetylcholine inhibitor. Novartis. Commercialized. Molecular mechanism
FK-508 Fujisawa Pharmaceutical Co Ltd Phase II
GABA inverse agonist Marion Merrell Dow (also depression) Phase II
inverse GABA agonist Marion Merrell Dow (also depression) Phase II
Galanthamine Galantamine ...Acetylcholinesterase inhibitor.....J Pharmacol Exp Ther 1996 May;277(2):728-738. Phase III (Jansen Pharmaceutica & Shire Pharmaceuticals) Molecular mechanism. Commercialized
Galanthamine derivatives Hoechst Marion Roussel; Waldheime Pharmazeutika AChE inhibitor. Phase III
Ginkgo biloba .Amélioration mise en évidence par plusieurs essais thérapeutiques: JAMA 1997 Oct 22;278(16):1327-1332
Sponsored by National Institute of Mental Health (NIMH) Purpose
The purpose of this study is to evaluate the effectiveness of donepezil (Aricept)
for the treatment of mild cognitive impairment (MCI) in elderly adults. This
study will also determine whether adding ginkgo biloba extract (GBE) enhances
the effects of donepezil.
Condition Treatment or Intervention Phase
Cognition Disorders
Alzheimer Disease Drug: Donepezil
Drug: Ginkgo Biloba Extract Phase IV
HALOPERIDOL
Alzheimer's patients with behavioral problems (e.g., sleep disturbance, agitation) and/or psychosis are commonly treated with antipsychotic medications like haloperidol. This study focuses on the treatment of behavioral symptoms in Alzheimer's disease with haloperidol and whether long term treatment is necessary. Phase I, Phase II
HuperzineA ....Exhibits anticholinesterase activity and is now under investigation as potential Alzheimer disease medication.
HYDERGINE
As in an earlier systematic review, we found hydergine to show significant
treatment effects when assessed by either global ratings or comprehensive rating
scales (based here on a smaller set of trials than in the earlier published
systematic review because trials were required to have data that could conform
with MetaView, the Cochrane Collaboration statistics software). The small number
of trials available for analysis, however, limited the ability of subgroup analyses
to identify statistically significant moderating effects.Unfortunately, most
of the randomized, double-blind, and placebo-controlled trials of hydergine
were conducted and published before the advent of consensus-based diagnostic
standards of dementia in 1984; therefore diagnostic criteria were less specific.
As a result, uncertainty remains regarding hydergine's efficacy in dementia.
Citation: Olin J, Schneider L, Novit A, Luczak S. Hydergine for dementia (Cochrane
Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.
The purpose of this study is to determine whether short-term use of the drugs ibuprofen and lovastatin affects levels of a protein called beta-amyloid in people who are at risk for developing Alzheimer's Disease (AD). Condition Phase Alzheimer Disease Phase IV
Idebedone. Takeda Chemical Industries Ltd. Lipid peroxidase inhibitor, nootropic agent. Awaiting approval
INDOMETHACIN
On the basis of this one trial and subsequent analysis of data as reported
by the authors, indomethacin cannot be recommended for the treatment of mild
to moderate severity Alzheimer's disease. At doses of 100-150 mg daily, serious
side effects will limit its use.
Citation: Tabet N, Feldman H. Indomethacin for the treatment of Alzheimer's
disease patients (Cochrane Review). In: The Cochrane Library, Issue 3, 2003.
Oxford: Update Software.
Lazabemide Hoffmann- La Roche (also Parkinson's) . MAO-B inhibitor.Awaiting approval
LEUPROLIDE
Sponsored by Voyager Pharmaceutical Corporation Purpose
ALADDIN is a research study to investigate the safety and effectiveness of leuprolide
(a hormone drug) to improve the cognitive function and slow the progression
of Alzheimer's disease (AD). In women leuprolide is commonly used to treat hormone
related conditions such as endometriosis and uterine fibroids. The study will
include treatment of women 65 years and older with mild to moderate Alzheimer's
disease who reside in the community.
Condition Treatment or Intervention Phase
Alzheimer Disease Drug: Leuprolide acetate Phase II
Levacecarnine Hoffman-La Roche Phase III
Lithium: To inhibit GSK3 beta, a kinase that overphosphorylates Tau
LOVASTATIN
The purpose of this study is to determine whether short-term use of the drugs
ibuprofen and lovastatin affects levels of a protein called beta-amyloid in
people who are at risk for developing Alzheimer's Disease (AD).
Condition Phase
Alzheimer Disease Phase IV
LY 246078 Eli Lilly Phase II (see Xanomeline)
LY451395 in Patients with Probable Alzheimer's Disease
This study is currently recruiting patients. Sponsored by Eli Lilly and Company
Purpose
Study of an investigational medication for the treatment of Alzheimer's Disease
in patients who are not taking Aricept, Reminyl, Exelon.
Condition Treatment or Intervention Phase Alzheimer's Disease Phase
II
MAO-B inhibitor Marion Merrell Dow (also Parkinson's) Phase II
MDL 26,479 (see 26,479)
MDL 73,745 (see 73,745)
Memolog (nebracetam) Boehringer
Ingelheime Gmbh Waiting approval Improving mental performance in
Alzheimer's disease
Metrifonate. Bayer AG. Acetylcholine inhibitor. Stopped. Problems.
Site Alzheimer Research Forum Molecular mechanism
Mentane (velnacrine maleate) Hoechst-Roussel Phase III application submitted
Milameline (CI-979) Warner-Lambert Co. Phase III M1 agonist
Montirelin Gruenenthal Gmbh ACh release stimulator, TRH agonist Phase III
NBI-4001 Neurocrine Biosciences Phase II
Nebracetam Boehringher Ingelheim Corp Non-NMDA antagonist Awaiting approval
Nefiracetam Daiichi Seiyaku Co Ltd Ach agonist, Ca channel opener: acting on presynaptic nicotinic Acetylcholine receptors. Awaiting approval
Neotrophin (AIT-082) purine derivative that enhances Nerve Growth Factor.: Websites see AIT 082
NICERGOLINE
The clinical studies on nicergoline were carried out with diverse criteria
and modalities of evaluation. Despite this, the 14 studies included in this
review, have presented generally consistent results. Results of this meta-analysis
provide some evidence of positive effects of nicergoline on cognition and behaviour
and these effects are supported by an effect on clinical global impression.
There was some evidence that there were increased risk of adverse effects associated
with nicergoline. These results were obtained on older patients with mild to
moderate cognitive and behavioural impairment of various clinical origins, including
chronic cerebrovascular disorders and Alzheimer's dementia. The few studies
specifically performed on patients with Alzheimer's disease were performed with
too few people to give a definitive answer to the questions concerning the use
of nicergoline for this form of dementia.This drug has not been evaluated using
current diagnostic categories such as MCI or in association with therapeutic
agents of different nature such as cholinesterase or antioxidant drugs.
Citation: Fioravanti M, Flicker L. Nicergoline for dementia and other age associated
forms of cognitive impairment (Cochrane Review). In: The Cochrane Library, Issue
3, 2003. Oxford: Update Software.
NSAIDs nonsteroidal antiinflammatory drugs
NS-105 Nippon Shinyaku Co Nootropic agent, ACh/GABA modulator
Oestrogènes (estrogenes)
NEM Cephalon Inc. preclinical
NeoTrofin see AIT-082
Nimotop (nimodipine) Miles Inc. Pharmaceutical Division Phase III
Olanzapine Quetiapine Risperidone Citalopram
The study is for people with Alzheimer's disease who are having trouble with their thinking or behavior. In particular, this study is trying to find out the best treatment for people who have hallucinations (seeing or hearing things that aren't there), delusions (false beliefs), or agitation
Ondanserion Glaxo Phase III
P10358, a novel, orally active acetylcholinesterase inhibitor J Pharmacol Exp Ther, 1997, 280:710-720
PIRACETAM
At this stage the evidence available from the published literature does not
support the use of piracetam in the treatment of people with dementia or cognitive
impairment. Although effects were found on global impression of change, no benefit
was shown by any of the more specific measures.There is a need for further evaluation
of piracetam by :1) Obtaining the data from the identified studies for an individual
patient database review,2) Performing a randomized trial of piracetam in patients
with diagnoses made by currently accepted diagnostic criteria. The trial should
extend over for a period of at least 6 months and preferably longer. Specific
cognitive instruments which are sensitive to change, Clinician Global Impression
of Change, levels of dependency and caregiver quality of life scales should
also be incorporated in such a study.
Citation: Flicker L, Grimley Evans J.. Piracetam for dementia or cognitive impairment
(Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.
Physostigmine (see Synapton)
Propentofylline Hoechst Marion Roussel Alzheimer and vascular dementia. PDE inhibitor. Awaiting approval. Some problems.
There is limited evidence that propentofylline might benefit cognition, global
function and activities of daily living of people with Alzheimer's disease and/or
vascular dementia. The meta-analyses reported here are far from satisfactory
as a summary of the efficacy of propentofylline, considering the unpublished
information on another 1200 patients in randomized trials that exists. Unfortunately
Aventis has been unwilling to correspond with the authors, significantly limiting
the scope of this review.
Citation: Frampton M, Harvey RJ, Kirchner V. Propentofylline for Dementia (Cochrane
Review). In: The Cochrane Library, Issue 3, 2003. Oxford: Update Software.
Quetiapine Risperidone Citalopram
The study is for people with Alzheimer's disease who are having trouble with their thinking or behavior. In particular, this study is trying to find out the best treatment for people who have hallucinations (seeing or hearing things that aren't there), delusions (false beliefs), or agitation.
Raloxifene, an estrogen-like medication approved by the Food
and Drug Administration for the treatment of osteoporosis, in improving memory
and the ability to live independently in postmenopausal women with Alzheimer's
disease.
Condition Treatment or Intervention Phase
Alzheimer Disease Drug: Raloxifene Phase II, Phase III
Reminyl ( galantamine) Acetylcholinesterase inhibitor.....J Pharmacol Exp Ther 1996 May;277(2):728-738. Phase III (Jansen Pharmaceutica & Shire Pharmaceuticals). Commercialized.
Risperidone Citalopram
The study is for people with Alzheimer's disease who are having trouble with their thinking or behavior. In particular, this study is trying to find out the best treatment for people who have hallucinations (seeing or hearing things that aren't there), delusions (false beliefs), or agitation
Rivastigmine (see Exelon) Molecular mechanism
Rosiglitazone
This study examines the use of insulin-sensitizing compounds, as therapeutic
agents for cognitive impairment in Alzheimer's disease.
Condition Treatment or Intervention Phase
Phase II
S12024 ..........phase IIb Development stopped. Problems of toxicity
sabcomeline SB 202026 SmithKline Beecham. Phase III. M1 partial agonist
SB 202026 (sabcomeline) SmithKline Beecham. Phase III. M1 partial agonist
Selegiline (Eldepryl) Somerset Inc MAO B inhibitor
SELENIUM
The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE)
prevention trial is an important addition to the Selenium and Vitamin E Cancer
Prevention Trial (SELECT). As a prevention trial, PREADVISE is trying to find
out if taking selenium and/or Vitamin E supplements can help to prevent memory
loss and dementia such as Alzheimer's disease.
Condition Treatment or Intervention Phase
Alzheimer Disease Drug: Vitamin E
Drug: Selenium Phase III
Simvastatin: CLASP is a research study to investigate the safety and effectiveness of simvastatin (a cholesterol lowering drug or statin) to slow the progression of Alzheimer's disease (AD). Statins are commonly used to treat high cholesterol levels, which increase the risk of heart disease and stroke.
SR 46559 Sanofi S.A Phase II
Suritozole (see 26,479 ) or MDL 26,479
Synapton (physostigmine salicylate) Forest Laboratories. Awaiting approval
tacrine (see Cognex, CI-970) Molecular mechanism
talsaclidine Boehringer Ingelheim
Corp M1 agonist Phase III
Vaccination, using synthetic amyloid peptideas antigen.
Excellent results on transgenic mice that develop amyloid plaques.
Phase I finished. Phase II stopped, due to aseptic meningoencephalitis. Several trials with passive and active immunisation are ongoing (Elan, Merck, etc).
Vin (see Wine)
VITAMIN E
The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE)
prevention trial is an important addition to the Selenium and Vitamin E Cancer
Prevention Trial (SELECT). As a prevention trial, PREADVISE is trying to find
out if taking selenium and/or Vitamin E supplements can help to prevent memory
loss and dementia such as Alzheimer's disease.
Condition Treatment or Intervention Phase
Alzheimer Disease Drug: Vitamin E
Drug: Selenium Phase III
-------------
There is insufficient evidence of efficacy of vitamin E in the treatment of
people with Alzheimer's disease. The one published trial of acceptable methodology
(Sano 1997) was restricted to patients with moderate disease, and the published
results are difficult to interpret. There is sufficient evidence of possible
benefit to justify further studies. There was an excess of falls in the vitamin
E group compared with placebo which requires further evaluation.
Citation: Tabet N, Birks J, Grimley Evans J, Orrel M, Spector A. Vitamin E for
Alzheimer's disease (Cochrane Review). In: The Cochrane Library, Issue 3, 2003.
Oxford: Update Software.
Wine (Bordeaux of course!!)
Source: 1993 Survey, "New
Medicines in Development for Older Americans,"
and PharmaBusiness, "What's in the pipeline". August
1996, NIH 1998
Anti-inflammatories.
AD
is a disease of general brain failure; augmenting only one
neurotransmitter system in the brain is not going to be
sufficient. Thus, other drug interventions are being investigated.
Dr Alzheimer described senile plaques as one of the pathologic
hallmarks of the disease. Late in the course of AD, there is an
inflammatory response around these plaques. Consequently, some of
the damage from the disease may arise from the inflammatory
response within the brain tissue. Patients who have been taking
nonsteroidal antiinflammatory drugs (NSAIDs) for other
indications seem to have a lower risk of developing Alzheimer's.
Furthermore, some case reports suggest that ibuprofen delays the
course of AD. Although the optimal dosage has not been
established, this author currently prescribes 400 mg bid for his
patients with AD. Of course, like other NSAIDs, ibuprofen can
cause GI or renal effects.
Estrogens.The debate over whether postmenopausal women should take estrogen has been raging for years--long enough for some of these women to become old enough to get AD. Some studies suggest that estrogen, in addition to protecting against heart disease and bone loss, protects against AD.[8] Estrogen also seems to slow the progression of AD in those who already have it. The mechanism underlying its possible prophylactic efficacy in AD is not known. Estrogen does serve as a trophic factor for ACh, and one study shows that patients on both estrogen and an AChE inhibitor fare better than do those on either treatment alone.[9] Unopposed estrogen therapy may increase the risk of uterine cancer, whereas data on the effect of estrogen on the risk for breast cancer are less clear.
A
review by Beverly N. Jones III, MD, John R. Absher, MD
Other drugs. Some data suggest that an antioxidant such as vitamin E, at a dosage of 2000 IU/day, slows AD progression.[10] In addition, since levels of monoamine oxidase (MAO) rise with aging, an MAO inhibitor (MAOI) might logically serve as an anti-aging pill. In fact, preliminary evidence suggests that selegiline (Eldepryl), a selective MAOI that does not require a tyramine-free diet, can also be helpful in treating AD (N Engl J Med, 1997, 336:1216-1222. MAOIs should not be combined with selective serotonin reuptake inhibitors (SSRIs), meperidine, or general anesthetics.
Rev Neurol (Paris) 1997 Apr;153(3):185-192
Unite de Recherche Epidemiologique, INSERM U 330, Universite de Bordeaux II, France.
Alcoholism is a possible cause of dementia, mainly through associated nutritional deficiencies and, rarely, through acute direct toxicity. However alcohol consumption was not found to be a risk factor in previous epidemiologic studies. We prospectively studied 3,777 community residents aged 65 and over, in the districts of Gironde and Dordogne. Average daily alcoholic consumption was recorded at baseline. Incident cases of dementia and Alzheimer's disease were screened at follow-up with explicit criteria. At 3 years, 2,273 subjects not demented at baseline were still available for follow-up. Wine was the only alcoholic beverage reported by more than 95 p. 100 of regular drinkers. In the 318 subjects drinking 3 to 4 standard glasses per day (> 250 and up to 500 ml), categorized as moderate drinkers, the crude odds ratio (OR) was 0.18 for incident dementia (p < 0.01) and 0.25 for Alzheimer's disease (p < 0.03), as compared to the 971 non-drinkers. After adjusting for age, sex, education, occupation, baseline MMSE and other possible confounders, the ORs were respectively 0.19 (p < 0.01) and 0.28 (p < 0.05). In the 922 mild drinkers (< 1 to 2 glasses per day) there was a negative association only with AD, after adjustment (OR = 0.55; p < 0.05). The inverse relationship between moderate wine drinking and incident dementia was explained neither by known predictors of dementia nor by medical, psychological or socio-familial factors. Considering also the well documented negative associations between moderate wine consumption and cardiovascular morbidity and mortality in this age group, it seems that there is no medical rationale to advise people over 65 to quit drinking wine moderately, as this habit carries no specific risk and may even be of some benefit for their health. Advising all elderly people to drink wine regularly for prevention of dementia would be however premature at this stage.
PMID: 9296132, UI: 97441913
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