Current Neurotransmitter Strategies in AD Drug Development

  • Paul T. Francis
  • J. Tracy Alder
  • Kate L. Cole
  • Kirsten E. Heslop
  • Stephen L. Minger
  • Maria J. Ramirez
Chapter
Part of the Advances in Behavioral Biology book series (ABBI, volume 49)

Abstract

Detection of very substantial deficits in the enzyme responsible for the synthesis of acetylcholine, choline acetyltransferase (ChAT), in the neocortex (Bowen et al., 1976; Davies and Maloney, 1976; Perry et al., 1977) and correlation with dementia rating (Francis et al., 1985) provided the first rational therapeutic target for the treatment of Alzheimer’s disease (AD). Current drug therapies in use and under development for the treatment of AD have, therefore, tended to concentrate on restoring the cholinergic deficits associated with the disease. Continuing research is beginning to identify other possible therapeutic approaches to treating AD. Cholinoceptive glutamatergic pyramidal neurones have been proposed to play a central role in both the pathogenesis and cognitive impairment associated with AD. Enhancing the activity of these cells may provide a further target for therapeutic strategies to combat the progression of the disease (Francis, 1996). The development of new drugs for the treatment of affective disorders in general could also be applied to the specific area of AD drug development to enable treatment of behavioural changes associated with AD, including depression, anxiety, psychosis and overactivity (Hope and Fairburn, 1992). These abnormal behaviours are often identified by carers as the most difficult aspect of the disease to cope with and usually determine admission to long-stay residential care with the associated costs. The neurochemical basis of such symptoms in AD patients has only recently received significant attention (Esiri, 1996). These alternative neurotransmitter-based strategies for the treatment of AD, in addition to the current use of cholinomimetics with their limited success in clinical trials, forms the basis of this review on AD drug development.

Keywords

Nerve Growth Factor Basal Forebrain Cortical Pyramidal Neurone Paroxetine Binding Dorsal Raphe Neurone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Paul T. Francis
    • 1
  • J. Tracy Alder
    • 1
  • Kate L. Cole
    • 1
  • Kirsten E. Heslop
    • 1
  • Stephen L. Minger
    • 1
  • Maria J. Ramirez
    • 1
  1. 1.Dementia Research Laboratory Division of Biochemistry and Molecular BiologyUnited Medical and Dental Schools of Guy’s and St. Thomas’ HospitalsLondonUK

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