Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies.
BACKGROUND
Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound resulting from the reaction between dimethylaminoethanol (an indirect precursor of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid having procholinergic properties and promnesic effects in both animals and man).


OBJECTIVE
The present study undertook preclinical and clinical evaluations to test a potential therapeutic utility for DMAE p-Glu in cognitive impairments related to central cholinergic deficit.


METHODS
In preclinical study, DMAE p-Glu was studied in rats by intracerebral microdialysis in conscious freely moving animals, on performance of rats in the Morris water maze test of spatial memory, and on the deficit in passive avoidance behavior induced by scopolamine. The clinical study examined the effect of DMAE p-Glu on cognitive deficits induced by an intravenous injection of scopolamine in healthy young male subjects.


RESULTS
In rat experiments, DMAE p-Glu increased the extracellular levels of choline and acetylcholine in the medial prefrontal cortex, as assessed by intracerebral microdialysis, improved performance in a test of spatial memory, and reduced scopolamine-induced memory deficit in passive avoidance behavior. Clinical study results show that scopolamine induced a memory deficit and that DMAE p-Glu produced a significant positive effect on scores in the Buschke test, as well as a slight but significant difference on choice reaction time.


CONCLUSIONS
These results indicate that DMAE p-Glu reduces the deleterious effect of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p-Glu might be effective in reducing memory deficits in patients with cognitive impairment.
Blin
Olivier
O
CIC-UPCET, UMR CNRS-Université de la Méditerranée 6193, Hôpital de la Timone, 13385, Marseille cedex 5, France. olivier.blin@ap-hm.fr
Audebert
Christine
C
Pitel
Séverine
S
Kaladjian
Arthur
A
Casse-Perrot
Catherine
C
Zaim
Mohammed
M
Micallef
Joelle
J
Tisne-Versailles
Jacky
J
Sokoloff
Pierre
P
Chopin
Philippe
P
Marien
Marc
M
D000328:Adult; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D018592:Cross-Over Studies; D003642:Deanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004311:Double-Blind Method; D005971:Glutamates / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D017551:Microdialysis / Q000379:methods; D018727:Muscarinic Antagonists / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012601:Scopolamine / Q000633:toxicity; D055815:Young Adult
D005971:Glutamates; D018727:Muscarinic Antagonists; C548477:dimethylaminoethanol pyroglutamate; D003642:Deanol; D012601:Scopolamine