ACETYL-L-CARNITINE IN ALZHEIMER-DISEASE - A SHORT-TERM STUDY ON CSF NEUROTRANSMITTERS AND NEUROPEPTIDES

Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of cent ral nervous system (CNS)-related effects, even though a clear pharmaco logical action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal f luid (CSF) and plasma biological correlates of ALCAR effects in AD aft er a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly high er than the ones at baseline, reflecting a good penetration through th e blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and thei r metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MH PG, dopamine, choline). Among CSF peptides, while corticotropin-releas ing hormone and adrenocorticotropic hormone remained unchanged, beta-e ndorphins significantly decreased after treatment; plasma cortisol lev els matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperac tivity. At present, no clear explanation can be proposed for the speci fic mechanism of this action.