CHOLINERGIC PHYTOCHEMICALS - FROM MAGIC TO MEDICINE

The decline in cortical cholinergic activity in aging and degenerative diseases associated with dementia is, in conjunction with increasing genetic and molecular complexity, one of the most consistent observati ons in psychopathology. Numerous plants synthesize compounds, interact ing with cholinergic systems which have been of value in exploring the role of the cholinergic system in aging and dementia. These chemicals deter predators by interfering with autonomic, central nervous or neu romuscular systems. The original hypothesis that memory loss in Alzhei mer's disease relates to a central cholinergic deficiency was partly b ased on the experimental induction of related cognitive impairments in normal individuals exposed to the naturally occurring muscarinic anta gonist scopolamine. Long before this, in ancient Greece, henbane (cont aining alkaloids such as atropine and scopolamine) was used to mimic ' dementia' and provoke prophesy. The tendency of such tropane alkaloids to induce hallucinations is consistent with low neocortical activitie s and the high incidence of psychotic features in Dementia with Lewy b odies (DLB). Other plant derived alkaloids such as physostigmine and g alanthamine, inhibiting acetylcholinesterase, are among those includin g the synthetic chemical tacrine, being tested in dementia therapy. Co gnitive enhancement, although significant, is limited and antipsychoti c effects may be more prominent. The recent discovery of brain nicotin ic receptors and the neuroprotective role of the tobacco alkaloid nico tine provides a further dimension to cholinergic therapy in retarding the neurodegenerative process. The potential for new cholinergic drug development based on the rich biodiversity of plant chemicals and prin ciples of ethnobotany, in the context of modem pharmacology, is still largely unexplored in age-related mental disorders. Several plant spec ies reputed to improve memory in European medicinal plant encyclopaedi as have cholinergic activities which may be therapeutically relevant.