Alzheimers disease is an irreversible neurodegenerative disease, characterized by cognitive decline and loss of memory. Although a number of neurotransmitters are affected, the loss of cholinergic neurons is considered the h allmark of Alzheimer's disease. C urrent therapy for Alzheimer's disease involves the use of acetylcholinesterase inhibitors. Although these agents do improve cognition and memory in the Alzheimer's patient, they do not halt the loss of cholinergic neurons and thus, the progression of the disease. Choline possesses neuroprotective activity via activation of alpha 7 nicotinic receptors. However, choline is a poor drug candidate due to its high polarity, which hinders CNS penetration, and its low potency (ED50 = ~1mM). In order to explore the possibility of improving both the potency and the brain penetration of choline, we have synth esized a series of compounds based on the choline structure. Two series of compounds were synthesized, the N -substituted benzyl-N-Methyl ethanolamines and the N-benzyl-N-hydroxyethyl piperazines. These compounds were evaluated in PC12 cells for their ability to protect against neuron growth factor (N GF) deprivation (cytoprotection assay) and their ability to interact with the high affinity choline transporter. The 3 -fluorobenzyl derivative was the most potent of the N-methyl ethanolamine series, having an ED50 for cytoprotection of 30 nM . Nicotine, which also possessed neuroprotection activity, was found to have an ED50 of ~60 nM. The piperazine derivatives evaluated were found to be less potent tha n nicotine, but still showed good overall activity.