Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies
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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).
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.
Materials and 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.
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.
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.
KeywordsDimethylaminoethanol pyroglutamate Scopolamine Cognitive tests Human volunteers Rat Microdialysis
The authors gratefully acknowledge the excellent technical assistance of Martine Mas (CRPF) in performing the rat microdialysis experiments and HPLC analyses and Pascale Petiot (CRPF) in performing the rat behavioral experiments. Experiments comply with the current laws of the country as they were performed.
- Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218Google Scholar
- Buschke H (1973) Selective reminding for analysis of memory and learning. J Verbal Learn Verbal BehavGoogle Scholar
- Drago F, Continella G, Valerio C, D’Agata V, Astuto C, Spadaro F, Scapagnini U (1987) Effects of pyroglutamic acid on learning and memory processes of the rat. Acta Therapeutica 13:587–594Google Scholar
- Ebert U, Oertel R, Kirch W (2000) Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects. Int J Clin Pharmacol Ther 38:532–531Google Scholar
- Erskine FF, Ellis JR, Ellis KA, Stuber E, Hogan K, Miller V, Moore E, Bartholomeusz C, Harrison BJ, Lee B, Phan KL, Liley D, Nathan PJ (2004) Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans. Hum Psychopharmacol 19:503–509CrossRefPubMedGoogle Scholar
- Friedman P (1991) GB-STAT: Computer-aided statistics & graphics, ver 3.0. Silver Spring: Dynamic Microsystems, IncGoogle Scholar
- Kolb B, Tees RC (1990) The cerebral cortex of the rat. MIT Press, CambridgeGoogle Scholar