Nicotinic receptor, galantamine and Alzheimer disease

Population aging has increased and will drastically increase the prevalence of Alzheimer disease. The disease develops inexorably towards a syndrome of marked cognitive impairment, accompanied of emotional alterations and profound changes of personality. The patient loses its autonomy, and requires special attention of caregivers; this leads to a decrease of the quality of life, not only of the patient but also of its caregivers and family. The reduction of the number of functional nicotinic receptors in brain keeps pace with neurological symptoms and the severity of the disease (cholinergic theory of Alzheimer disease). There is a pleyade of data and observations reinforcing the idea that improving cholinergic neurotransmission is an investment in memory. Up to now, although with limited success, this improvement has been achieved only with the reversible inhibitors of acetylcholinesterase tacrine, rivastigmine and donepezil, available in the clinic since a few years. The last approved has been galantamine that in spite of being a modest inhibitor of acetylcholinesterase, improves memory (ADAS-cog test) and slows down cognitive impairment of Alzheimer patients. To explain this therapeutic effect, a second mechanism of action for galantamine has been suggested, the positive allosteric modulation of presynaptic nicotinic receptors, that will favour the release of acetylcholine and other neurotransmitters involved in memory formation. Furthermore, galantamine possesses neuroprotectant antiapoptotic effects, according to recent data from our laboratory. These effects provide new ideas and therapeutic targets that might help to find novel and efficacious treatments for patients suffering Alzheimer disease.