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Strategies and new aspects in the pharmacology of drugs for the treatment of senile dementia
Author(s) -
Schmidt Joachim,
Fischer HansDieter,
Wustmann Christian
Publication year - 1988
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430140317
Subject(s) - neuroscience , dementia , neurotransmission , piracetam , medicine , pharmacology , drug , cholinergic , synaptic plasticity , psychology , disease , receptor
Rational therapeutic strategies can be derived only from an understanding of the etiopathogenetic processes leading to dysfunction in the demented brain. Senile dementias (SD) of different origins are associated with biochemical changes in functionally important transmission systems, in energy metabolism, and in synthesis of macromolecules. Much evidence supports a particularly important role of dysfunction in central cholinergic mechanisms. Recent results have furnished encouraging indications that changes in synaptic efficiency and plasticity are integrated to a considerable degree. At present, the pharmacological manipulation of clinical symptoms and impaired functions is the basis for rational strategies in the development of drugs for the treatment of SD. On the basis of present knowledge, the following strategies can be considered: (1) drugs to prevent underlying etiopathogenetic processes (antioxidants, aluminium chelating agents, etc.); (2) enhancers of cerebral neurotransmission; (3) cerebral metabolic enhancers (nootropics and related drugs); (4) modulators of synaptic efficiency and plasticity; (5) nooanaleptics; (6) regulators of cerebral circulation; and (7) symptomatic therapy of associated functional mental disorders. The improvement of neuronal metabolism and synaptic transmission are presently the most important strategies in drug development. Nootropics and related drugs fulfill two aspects in the pharmacotherapy of SD: they are cerebral metabolic enhancers and they improve cerebral synaptic transmission processes. In eight of these functions, the relationship between lipid metabolism and cellular Ca ++ homeostasis also may be of special functional importance. For the development of further strategies, more detailed knowledge about the pathogenesis of SD and further experimental modeling of the etiopathogenetic and neuropathological processes underlying SD of different origins are required.