FUTURE MEDICATION IN ALZHEIMERS DISEASE

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FUTURE MEDICATION IN ALZHEIMER S DISEASE

• H. Allain, S. Schück, N. Mauduit,
• M. Djemaï
• Thessaloniki, Greece,
• Jan 2000

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OUR PROPOSAL IS THE FOLLOWING

• Summarize the therapeutics of today
• Try to improve our strategies
• Have a look at the tomorrow drugs
• To review the research in basic pharmacology

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THE THERAPEUTICS OF TODAY (I)

• The specific compounds
• Anticholinesterasics
• The unspecific compounds
• Nootropics Piracetam, Ginkgo
• Antioxidants Tocophérol, Sélégiline
• Psychotropics Antipsychotics
• Estrogens

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IMPROVEMENT OF OUR STRATEGIES

• Drug combination
• 2 anticholinesterasics
• Antioxidants
• Nootropics
• Use of psychotropics
• Stage of the disease/symptoms
• What teaches pharmacoepidemiology ?

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DRUGS USE IN THERAPEUTICS (1)222 patients with AD
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DRUGS USE IN THERAPEUTICS (2) 222 patients with
AD
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ANTICHOLINESTERASICS
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THE APPROACH BY SYMPTOMS

• 1 - BPSD
• An example Tiapride in agressivity and agitation
  in dementia
• 2 - The pharmacology of cognition
• AD is the paradigm of a cognitive disorder

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PHARMACOLOGY OF COGNITION ...

• Memory and memories
• Learning
• Language
• Reading
• Decision-making and so on ...

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AND TOMORROW ?
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THE THERAPEUTICS OF TODAY (II)
MMS Severity
?
Psychotropics Antidepressants (avoid tricyclics)
25-
Antioxidants
?
Anticholinesterasics
Antipsychotics Risperidone Tiapride
10-
Time
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DRUGS (AND THEORIES) DROP-OUT
2000
1990
Metrifonate propentofylline
Antibiotics (bacterias, virus)
Free radicals
SBXanomeline and muscarinic agonist (M1)
Celocoxib (inflammation)
Anti ? secretase Anti TAU
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NOTHING NEWPK/PD STUDIES
Y f ( x)
Cognition Behaviour Daily living Prevention
complex
Drug concentration in plasma and brain
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TROPHIC FACTORS

• Endogenous factors or similar
• Synthetic compounds
• Anti-apoptose drugs
• Real pathophysiology drugs

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PRESENILIN INHIBITORS

• New agent
• great therapeutic target (presenilins)
• diminishing ? secretase activity
• Notch signalling / T cells
• RCT ?
• Risks
• interference with haematopoiesis
• leukaemia

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TIAGE STUDY (1)

• Randomized clinical trial
• 3 parallel groups (tiapride, haloperidol, placebo
• 306 patients
• mild or moderate dementia (DSM III R)
• behavioural troubles (MOSES)
• Multidimensional Observation Scale for the
  Elderly Subjects irritability agressiveness

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TIAGE STUDY (2)

• Outcomes
• MOSES and global improvement (CGI)
• significant decrease for agressiveness
• tiapride not different from haloperidol
• better tolerated
• fewer extrapyramidal symptoms
• comparison with risperidone

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INFORMATION PROCESSING MODEL OF COGNITION

• Environment Attention Cognition
  Emotion
• Reward
• Behaviour Responses
• All those steps are within the brain

Motivation
Memory
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Biologie moléculaire de l apprentissage et de la
mémorisation
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AD AND OXIDATIVE STRESSMarkesbery W.R. Arch
Neurol 1999 56 (12)

• Lipid peroxidation
• Protein oxidation
• DNA oxidation
• Glyco oxidation
• Endogenous antioxidants
• Transgenic mice
• ? Neurocytoprotective agents ?

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CONCLUSION

• Pharmacological approaches of CNS diseases
  through cognitive processes
• Quick switch from a receptor tointelligence!
• Decision and choice of drugs
• Future new drugs