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 central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels 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 hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action.
Bruno
G
G
Dipartimento di Scienze Neurologiche, Università di Roma La Sapienza, Italy.
Scaccianoce
S
S
Bonamini
M
M
Patacchioli
F R
FR
Cesarino
F
F
Grassini
P
P
Sorrentino
E
E
Angelucci
L
L
Lenzi
G L
GL
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002331:Carnitine / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D010455:Peptides / Q000134:cerebrospinal fluid; D013997:Time Factors; D016896:Treatment Outcome
D018377:Neurotransmitter Agents; D010455:Peptides; D002331:Carnitine; D004298:Dopamine