Natural products and derivatives affecting neurotransmission relevant to Alzheimer's and Parkinson's disease.
The two major neurodegenerative diseases Alzheimer's disease (AD) and Parkinson's disease (PD) are characterised by low levels in the brain of the neurotransmitters acetylcholine (ACh) and dopamine (DA), respectively. Clinical treatment of these two conditions is palliative and relies, in most cases, on improving stimulation at the relevant receptors by either increasing levels of the endogenous neurotransmitter or by the use of substances which have a similar agonist response. Natural products continue to provide useful drugs in their own right but also provide templates for the development of other compounds. The major advances in the treatment of AD have been the use of acetylcholinesterase inhibitors such as galantamine, huperzine A, physostigmine and its derivatives to increase the levels of ACh rather than the use of cholinergic compounds, although compounds with nicotinic properties have attracted some interest. In contrast, the treatment of PD has relied on the elevation of DA levels by use of L-DOPA, its precursor, and by the administration of dopaminergic agonists, especially the ergot alkaloid derivatives. The use of inhibitors of enzymes that cause breakdown of DA is an avenue which is being explored. As well as the major natural products of clinical interest, the paper discusses the chemistry, activity and usage of the constituents of plants used in traditional medicine for the treatment of diseases presenting symptoms similar to those characteristic for Alzheimer's or Parkinson's disease.
Houghton
Peter J
PJ
Department of Pharmacy, King's College London, London, UK. peter.houghton@kcl.ac.uk
Howes
Melanie-Jayne
MJ
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D018377:Neurotransmitter Agents / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D010936:Plant Extracts; D000109:Acetylcholine; D004298:Dopamine