Authors: Richard T Reid Marwan N Sabbagh
Publish Date: 2008/08/26
Volume: 115, Issue: 10, Pages: 1437-1444
Abstract
Cholinesterase inhibitors ChEIs are the mainstay of treatment for AD but differ by secondary mechanisms of action We determine the effects of subchronic dosing of ChEIs on α7 and nonα7 nAChRs and determine if differences can be observed between them Sprague–Dawley rats were administered donepezil galantamine rivastigmine at two doses each in saline SQ twice daily or with nicotine 04 mg/kg as a positive control After 14 days the animals were sacrificed and the levels of nAChRs were measured using 3HEPI to measure nonα7 nAChRs and 3HMLA to measure α7 nAChRs In the cortex all compounds tested at the higher doses significantly increased the levels of both 3HEPI and 3HMLA In the hippocampus all compounds significantly increased 3HEPI but had no effect on 3HMLA binding No effects were observed in the striatum with treatment There were no differences observed among the ChEIs In cell cultures none of the ChEIs increased nonα7 or α7 receptor binding Treatment with ChEIs result in similar increases in receptor levels which suggest that the increases in nAChRs may be due simply to the increases in synaptic levels of acetylcholineDisclosures Dr Reid has nothing to disclose Dr Sabbagh is on the speaker’s bureau for Pfizer Eisai Forest and Novartis He is a consultant for Lilly and Eisai Dr Sabbagh receives clinical research funding from Eisai Pfizer GSK Novartis Avid Wyeth Lilly Medivation Abbott and Elan
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