[Trials and perspectives in pharmacotherapy of Alzheimer's disease].
The paper discusses therapeutical approaches to Alzheimer's disease on the basis of pathological mechanisms responsible for neurodegeneration. Amyloid plaques called also senile plaques situated extracellularly cause loss of neurons, especially cholinergic neurons, that begin in Nucleus of Meynert. However, recent evidence from postmortem brain and fibroblast studies suggests that both adenylyl cyclase and phosphatidylinositol hydrolysis signal transduction cascades are disrupted in AD. Such disruption may limit cholinergic pharmacotherapy. Other disorders, like disturbances in releasing Neuronal Growth Factor (NGF), oxidative stress, free Ca 2+, neuroimmunologic reactions are also important in AD brain changer. Only use of acetylcholine inhibitors: tacrine, donepezil and Gingko Biloba as well as nimodipine improved mental functions (MMSE screening). Neuroprotection of selegiline and NGF was observed. Behavioral symptoms often associated with dementia, like depression, anxiety, irritability, delusions, aggressiveness were treated with: olazepine, risperidone, haloperidol, clozapine, fluoxetine, paroxetine, sertraline, trazodon, dezypramine, lithium, benzodiazepines, carbamazepine and valproic acid. Drugs with strong anticholinergic effects, such as amitriptyline or imipramine should not be administered. Future studies on therapy to regulate metabolism of amyloid precursor-beta-APP are necessary to discover new efficient strategies.
Kieszek
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Zakładu Farmakologii Katedry Farmakologii AM w Lodzi.
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000175:diagnosis; D006801:Humans; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism; D009483:Neuropsychological Tests
D002800:Cholinesterase Inhibitors; D020932:Nerve Growth Factor