Wednesday, February 3, 2010

Alpha GPC


Description
Alpha GPC is a precursor to the essential neurotransmiter known as Acetylcholine[1][2]. It is one of the most bioactive forms[2], meaning that it is more readily absorbed and processed. In addition, it also has a stimulatory effect in regard to EEG response, which appears to be bell shaped in terms of dose to effect[3]. It was found to remove scopolamine-induced memory impairment[1], in addition to improving learning and memory in rats showing a deficit in these areas[4].

"Alpha GPC rapidly delivers choline to the brain across the blood-brain barrier and is a biosynthetic precursor of the acetylcholine neurotransmitter. Alpha GPC is derived from highly purified soy lecithin."[2]

Mechanism of Action
"Since, alpha-GPC administered IG is cleaved within the gut mucosal cells to glycerophosphate and free choline, it is tempting to speculate that this drug acts by increasing the ACh precursor pool. This view is supported also by the observation that alpha-GPC partially counteracts the decrease of brain ACh levels elicited by scopolamine administration. The effect is observed in the hippocampus and cortex, but not in the striatum."[6]
"The results show that the oral administration of alpha-GPC (100-300-600 mg/kg) induced a significant decrease in absolute spectral energy in the delta frequency band. A significant increase in absolute spectral energy in the beta frequency band was elicited by alpha-GPC at dose levels of 100 and 300 mg/kg, while the administration of a higher dose (600 mg/kg) of this compound resulted in the loss of response (bell-shaped dose-response curve)."[3]

Pharmacokinetics
"The peak effect is observed using 600 mg/kg IG, 5 h before training. The effect of the drug is long lasting (up 30 h) in accordance with its pharmacokinetic characteristics."[6]

Research
"The effects of L-alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced memory impairment and on brain acetylcholine (ACh) synthesis and release were investigated in rats. Oral administration of alpha-GPC 3 h before the behavioural test prevented the learning impairment induced by scopolamine given 30 min before the acquisition of a passive avoidance response. Similarly, retrograde amnesia induced by scopolamine, given immediately after acquisition training, was also completely reversed by the drug. These effects were dose-dependent with a maximum at 300 mg/kg. The mechanism of action of this compound was investigated by measuring hippocampal ACh synthesis and release both in vivo by means of the microdialysis technique and in vitro in tissue slices. alpha-GPC dose dependently increased ACh release with a maximum at 300 mg/kg. In addition, i.v. injection of [14C]alpha-GPC resulted in [14C]ACh formation. The data suggest that the behavioural effects of alpha-GPC may be related to its property to increase hippocampal ACh synthesis and release."[1]

"The effects of L-alpha-glycerylphosphorylcholine (alpha-GPC), a putative acetylcholine precursor, on the EEG power spetrum in rats were investigated. The results show that the oral administration of alpha-GPC (100-300-600 mg/kg) induced a significant decrease in absolute spectral energy in the delta frequency band. A significant increase in absolute spectral energy in the beta frequency band was elicited by alpha-GPC at dose levels of 100 and 300 mg/kg, while the administration of a higher dose (600 mg/kg) of this compound resulted in the loss of response (bell-shaped dose-response curve). No significant changes in the EEG power spectrum were found in rats treated with phosphatidylcholine (PC).
The present data, suggesting that the electrocorticographic (ECoG) activation elicited by alpha-GPC may be correlated with its stimulatory effect on brain acetylcholine release, further extend the pharmacological profile of this new cognition enhancer."[3]

"The phosphorylcholine precursor, L-alpha-glycerylphosphorylcholine (alpha-GPC), was injected at the dose of 100 mg/kg/day for 20 days to aged male rats of the Sprague-Dawley strain, 24 months old, showing a deficit of learning and memory capacity. The drug was also administered to rats with amnesia induced pharmacologically with bilateral injections of kainic acid into the nucleus basalis magnocellularis (NBM). Learning and memory capacity of the animals, studied with tests of active and passive avoidance behavior, was improved after treatment with alpha-GPC in all experimental groups. These results indicate that this drug affects cognitive mechanisms in the rat through an involvement of central neurotransmission.[4]"

"The aim of the present work was to compare the morphological changes occurring at the focus of experimental ischemic stroke treated with agents of the neurotrophic group (alpha-GPC, cerebrolysin), an agent with nootropic properties (piracetam), and a mixed-action agent (vinpocetin). Experiments were performed on 18 rats. Transient cerebral circulatory lesions (acute ischemia) were produced in the right hemisphere by clipping the stem of the innominate artery for 40 min. Light microscopic and electron microscopic studies were performed on fragments of cerebral cortex, brainstem, and cerebellum. Use of alpha-GPC and cerebrolysin increased the tolerance of neurons to ischemic damage and slowed the execution of the cell death program. Intracellular changes were seen and were interpreted as adaptive and reparative: these included folding of the nuclear membrane, abundance of polyribosomes, and endoplasmic reticulum and Golgi complex hypertrophy. These agents preserved the structures of the nuclear membranes and major cellular organelles. "[5]

"The present study investigates the effect of the administration of alpha-glycerylphosphorylcholine (alpha-GPC) on scopolamine-induced amnesia and on brain acetylcholine (ACh) levels and release in rats. The results indicate that alpha-GPC, when administered orally, reverses the amnesia caused by scopolamine in passive avoidance. The peak effect is observed using 600 mg/kg IG, 5 h before training. The effect of the drug is long lasting (up 30 h) in accordance with its pharmacokinetic characteristics. Since, alpha-GPC administered IG is cleaved within the gut mucosal cells to glycerophosphate and free choline, it is tempting to speculate that this drug acts by increasing the ACh precursor pool. This view is supported also by the observation that alpha-GPC partially counteracts the decrease of brain ACh levels elicited by scopolamine administration. The effect is observed in the hippocampus and cortex, but not in the striatum. Moreover, in ex vivo experiments, alpha-GPC is able to increase the amount of ACh released by rat hippocampus slices following potassium stimulation." [6]

References
[1] L-alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat.

[2] Wikipedia Entry: Alpha-GPC

[3] Effects of L-alpha-glycerylphosphorylcholine on the EEG power spectrum in the rat

[4] Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat.

[5] Changes at the focus of experimental ischemic stroke treated with neuroprotective agents 

[6] Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine

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