| Accueil | |
Therapy / Thérapeutique / Treatments
: Memantine, Vaccination, Reminyl/Galanthamine
Clinical trials ongoing; another address
Maladies neurodégénératives et Neuroleptiques
Médicaments d'aujourd'hui et de demain
please contact us if you have more information about new drugs
There is presently no cure
for Alzheimer's disease, but vaccination could change all that.
However, treatments are already available to help manage the
symptoms. Tacrine was prescribed to improve the memory impairment
in Alzheimer's disease, but it had to be administered under close
medical supervision because of side effects. New products with
less side effects are now at disposal (Aricept, Exelon, Memantine, Reminyl). Research
is ongoing, and other experimental treatments are currently being
tested in multicenter clinical drug trials.
These treatments are designed either to improve cognition or to
slow the rate of decline. There are also many medications
available for the behavioral symptoms associated with Alzheimer's
disease, including antidepressants and drugs to control the
agitation, anxiety and delusions. Antidepressants must be
administrated by skillfull neurologists, because some of these
drugs provoke catastrophic side effects.
Alzheimer's disease: an update
Treatment of Alzheimer's disease
A new product is not on the list? You have more information about a specific product, or drug, or trial ?
please tell me: delacourte@lille.inserm.fr
26,479 (Suritozole) Hoechst Marion Roussel Inc. Phase I/II.
Depression and Alzheimer's disease.
73,745 (MDL 73,745) Hoechst Marion Roussel Inc. Phase I (Trimethylsilylated trifluoromethyl ketones, a class of acetylcholinesterase inhibitors)
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
Amiridin . Nikken Chemical Co AChE inhibitor Phase III clinical
Ampalex Cortex Pharmacueticals Inc Phase I Memory deficiency
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
AVIVA (linopirdine) Du Pont Merck cognition enhancement Phase III
AXURA http://www.merz.com/ http://www.memantine.com
see Memantine
BC-PS (phosphatidylserine) Fidia
Pharmaceutical Phase II
beta sheet breakers: anti-amyloid. See the litterature from Ghizo.
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
A) Cognex (tacrine) Acetylcholine inhibitor. Warner-Lambert . Commercialized for hospitals
B) Cognex. The point of view of Parke-Davis Molecular mechanism
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,
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.
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
HuperzineA ....Exhibits anticholinesterase activity and is now under investigation as potential Alzheimer disease medication.
Idebedone. Takeda Chemical Industries Ltd. Lipid peroxidase inhibitor, nootropic agent. Awaiting approval
Lazabemide Hoffmann- La Roche (also Parkinson's) . MAO-B inhibitor.Awaiting approval
Levacecarnine Hoffman-La Roche Phase III
LY 246078 Eli Lilly Phase II (see Xanomeline)
MAO-B inhibitor Marion Merrell Dow (also Parkinson's) Phase II
MDL 26,479 (see 26,479)
MDL 73,745 (see 73,745)
Memantine: Sold in Germany. Antagonist
of NMDA receptors. Decreases the deleterious entry of calcium generated by
excitotoxic glutamatergic neurons. Good results on moderately to severe
Alzheimer patients:
Vendu en Allemagne. Donne des résultats significatifs pour les démences Alzheimer
modérées et sévères. Voir Mémantine
Memolog (nebracetam) Boehringer
Ingelheime Gmbh Waiting approval Improving mental performance in
Alzheimer's disease
Metrifonate. Bayer AG. Acetylcholine inhibitor. Awaiting approval. 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
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
Ondanserion Glaxo Phase III
P10358, a novel, orally active acetylcholinesterase inhibitor J Pharmacol Exp Ther, 1997, 280:710-720
Physostigmine (see Synapton)
Propentofylline Hoechst Marion Roussel Alzheimer and vascular dementia. PDE inhibitor. Awaiting approval. Some problems.
Reminyl ( galantamine) Acetylcholinesterase inhibitor.....J Pharmacol Exp Ther 1996 May;277(2):728-738. Phase III (Jansen Pharmaceutica & Shire Pharmaceuticals). Commercialized.
Rivastigmine (see Exelon) Molecular mechanism
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
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 in progress in USA and Europe,
including France.
Essai thérapeutique en cours.
Vin (see Wine)
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
|
