Overview
Alpha GPC (L-alpha-glycerylphosphorylcholine, choline alphoscerate) is a choline-containing phospholipid derivative described as a precursor in the biosynthesis of brain phospholipids and as a cholinergic precursor that increases the availability of acetylcholine3,6.
Preclinical studies have examined hippocampal acetylcholine synthesis and release, cholinergic transporters and receptors, protein kinase C translocation and inflammatory markers in rat brain1,2,3,4,5. It has also been examined in clinical research, including the ASCOMALVA trial6,7.
Mechanism of action
As described in the research literature
As described in the research literature, alpha GPC increased hippocampal acetylcholine release in rats, measured by in vivo microdialysis and in tissue slices, and radiolabelled alpha GPC gave rise to radiolabelled acetylcholine in rat studies, consistent with its use as a substrate for acetylcholine synthesis1.
A comparison with CDP-choline in rats reported region-specific changes in acetylcholine levels and in expression of the vesicular acetylcholine transporter (VAChT) and the choline transporter (CHT) across frontal cortex, striatum and cerebellum4. Other work reported protein kinase C translocation in rat cortex in vivo and in cortical slices2, and partial preservation of hippocampal muscarinic M1 receptor sites in aged rats3.
Research areas
What published studies have examined
Cholinergic transmission and scopolamine models
Rat studies examined scopolamine-induced impairment of passive avoidance learning and retrograde amnesia, together with hippocampal acetylcholine synthesis and release by microdialysis and in tissue slices1.
Sources [1]
Transporters, receptors and signalling
Muscarinic M1 and M2 receptors were examined by radioreceptor assay and autoradiography in the hippocampus of young, adult and aged rats3. Other rat studies measured VAChT and CHT expression by Western blot, ELISA and immunohistochemistry4, and protein kinase C activity in soluble and particulate fractions of brain tissue2.
Sources [2] [3] [4]
Neuroinflammation markers
A two-week rat study measured interleukin-1 beta, interleukin-6, TNF-alpha, ICAM-1 and VCAM-1 in the frontal cortex, hippocampus and cerebellum after choline or alpha GPC and reported no change in these markers5. An erratum to this paper was published in 2024.
Sources [5]
Clinical research
ASCOMALVA is a double-blind, multicentre, randomised trial designed to compare donepezil plus choline alphoscerate with donepezil plus placebo in Alzheimer's disease with ischaemic cerebrovascular injury, using cognitive, functional and behavioural assessments that include the MMSE and ADAS-cog7. A review from the same group summarises preclinical and clinical work6.
Sources [6] [7]
Specifications
- Molecular formula
- C8H20NO6P
- Molecular weight
- 257.22 g/mol
- CAS number
- 28319-77-9
- Form
- Measured units with a stated amount per unit, 30 to a resealable foil pouch
- Storage
- Store in a cool, dry place in the sealed pouch, away from direct light. The compound is hygroscopic, so keep the pouch closed between uses.
- Solubility and reconstitution
- Supplied ready to use: each unit is pre-measured, so no reconstitution is required.
References
- 1
L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat.
Sigala S, Imperato A, Rizzonelli P, et al. European Journal of Pharmacology, 1992.
PubMed 1319912 ↗DOI 10.1016/0014-2999(92)90392-h ↗
- 2
- 3
- 4
- 5
- 6
Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profile as cognition enhancing agent.
Traini E, Bramanti V, Amenta F Current Alzheimer Research, 2013.
PubMed 24156263 ↗DOI 10.2174/15672050113106660173 ↗
- 7
The ASCOMALVA trial: association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in Alzheimer's disease with cerebrovascular injury: interim results.
Amenta F, Carotenuto A, Fasanaro AM, et al. Journal of the Neurological Sciences, 2012.
PubMed 22959283 ↗DOI 10.1016/j.jns.2012.07.003 ↗