High occupancy of σ1 receptors in the human brain after single oral administration of donepezil: a positron emission tomography study using [11C]SA4503

The acetylcholinesterase (AChE) inhibitor donepezil is also a sigma(1) receptor agonist. We examined whether donepezil binds to a, receptors in the living human brain after a single oral administration. Dynamic positron emission tomography (PET) data acquisition using the selective sigma(1) receptor ligand [C-11]SA4503 was performed to evaluate quantitatively the binding of [C-11]SA4503 to at receptors in eight healthy male volunteers. Each subject had a PET scan before and after receiving a single dose of donepezil (5 or 10 mg). The binding potential of [C-11]SA4503 was calculated. Doses of 5 mg and 10 mg donepezil bound to a, receptors in the human brain with occupancies of similar to 60% and similar to 75%, respectively, in a dose-dependent manner. This study demonstrated that donepezil binds to sigma(1) receptors in the Living human brain at therapeutic doses. Therefore, sigma(1) receptors may be implicated in the pharmacological mechanism of donepezil in the human brain.