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

López, Clara; Govoni, Stefano; Battaini, F.; Bergamaschi, S.; Longoni, Aline; Giaroni, Cristina; Trabucchi, Marco

doi:10.1016/0091-3057(91)90040-9

Cited by 45 publications

(19 citation statements)

References 34 publications

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“…These results have been confirmed by clinical studies showing that scopolamine-induced amnesia in human volunteers was antagonized by alpha-GPC [Canal et al, 19911. As far as the bell-shaped dose effect relationship, Lopez et al [1991] suggested that the higher levels of the drug could lead to excess acetylcholine synthesis, triggering homeostatic mechanisms such as receptor desensitization or activation of presynaptic inhibitory receptors.…”

Section: Discussionmentioning

confidence: 99%

Effects of L‐alpha‐glycerylphosphorylcholine on the EEG power spectrum in the rat

Lacomba

Cagiano

Maci

et al. 1992

Drug Development Research

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The effects of L-alpha-glycerylphosphorylcholine (alpha-GPC), a putative acetylcholine precursor, on the EEG power spectrum in rats were investigated. The results show that the oral administration of alpha-GPC (1 00-300-600 mglkg) 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. 0 1992 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Effects of L‐alpha‐glycerylphosphorylcholine on the EEG power spectrum in the rat

Lacomba

Cagiano

Maci

et al. 1992

Drug Development Research

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Section: Discussionmentioning

confidence: 99%

“…The behavioral and neurochemical properties of alpha-GPC, a putative choline precursor, have been characterized [Lopez et al, 1991;Sigala et al, 19921. Alpha-GPC prevented impairment of acquisition of the passive avoidance response and disruption of memory consolidation, both induced by scopolamine [Lopez et al, 1991;Sigala et al, 19921. These effects were paralleled, at least at short times (3-5 hr), by a huge increase of ACh synthesis and release in the hippocampus and frontal cortex [Lopez et al, 1991;Sigala et al, 19921. Since drugs ameliorating learning and memory are usually administered chronically, here we investigated the effects of long-term treatment with alpha-GPC on hippocampal ACh release and on muscarinic receptor plasticity.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of muscarinic agonists [Haroutunian et al, 1985;Miyamoto et al, 1989;Nakahara et al, 19901, acetylcholinesterase inhibitors [Haroutunian et al, 1985;Summers et al, 1986;Gauthier et al, 19901, and acetylcholine (ACh) precursors [Bartus et al, 19801 on various models of memory impairment have been characterized. It has recently been shown that L-alpha-glycerylphosphorylcholine (alpha-GPC), a lecithin derivative containing a molecule of choline in its structure, antagonized scopolamine-induced impairment of learning and memory and increased both the synthesis and release of ACh in rat hippocampus and frontal cortex [Lopez et al, 1991;Sigala et al, 19921. Since drugs ameliorating learning and memory are usually administered for long periods of time, we investigated the effects of chronic treatment with alpha-GPC on the neurochemical parameters linked to hippocampal cholinergic transmission as ACh release and muscarinic cholinergic receptor density and function.…”

Section: Introductionmentioning

confidence: 99%

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Effects of chronic treatment with L‐alpha‐glycerylphosphorylcholine on hippocampal cholinergic transmission in the rat

Missale

Sigala

Rizzonelli

et al. 1992

Drug Development Research

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Missale, C., S. Sigala, P. Rizzonelli, E. Zanelli, and P. Spano: Effects of chronic treatment with L-alpha-glycerylphosphorylcholine on hippocampal cholinergic transmission in the rat. Drug Dev. Res. 27:277-286, 1992. L-alpha-glycerylphosphorylcholine (alpha-GPC) has been proposed for the treatment of age-related cognitive disturbances. In the rat the compound prevents the learning impairment and the retrograde amnesia both induced by scopolamine and this effect appears to be correlated with an increase of hippocampal acetylcholine production and release. Since drugs ameliorating learning and memory are usually administered for long periods of time, here we investigated the effects of chronic treatment with alpha-GPC on the neurochemical parameters linked to hippocampal cholinergic transmission. The data show that an increased [3H]acetylcholine (ACh) release was detectable in rats chronically exposed to alpha-GPC and killed 3 hr after the last administration, suggesting that tolerance did not develop in these experimental conditions. An alpha-GPC-induced selective desensitization of hippocampal muscarinic M-2 receptor function was also found. This event was characterized by a decreased responsiveness of adenylate cyclase to carbachol inhibition in the absence of changes in M-2 receptor density. This effect could be relevant in view of M-2 receptor presynaptic location and function in inhibiting ACh release. In contrast with M-2 receptor, M-1 receptor density and function were not significantly changed by the treatment. The present data suggest that alpha-GPC could be proposed as a useful drug for the chronic treatment of memory deficit. o 1992 Wiley-Liss, Inc.

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“…Preclinical pharmacological studies have demonstrated that aGPC facilitates learning and memory in experimental animals (Lopez et al 1991;Drago et af. 1992a & b), and decreases the age-dependent or the neurotoxin-induced morphological changes in the hippocampus and frontal cortex in the rat (Niglio e?…”

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confidence: 99%

Chronic L‐α‐Glyceryl‐phosphoryl‐choline Increases Inositol Phosphate Formation in Brain Slices and Neuronal Cultures

Nicoletti

Sortino

Casabona

et al. 1994

Pharmacology & Toxicology

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Repeated, but not single injections of L-alpha-glyceryl-phosphorylcholine (alpha GPC) significantly increased basal [3H]inositol monophosphate (InsP) formation in hippocampal, cortical, and striatal slices of male rats. The effect was dose-dependent and was accompanied by an increased incorporation of [3H]inositol into the phospholipid fraction. Incubation of brain slices with different neurotransmitter antagonists, such as atropine, prazosin, or L-2-amino-4-phosphonobutanoate (L-AP4) did not modify the increase in [3H]InsP formation produced by alpha GPC, suggesting that the effect is not mediated by an increased availability of a specific neurotransmitter. Similar results were obtained in cerebellar and cortico-striatal neurones in primary culture exposed to daily addition of alpha GPC since the second day of maturation in vitro. We suggest that alpha GPC treatment may result in an increased rate of phospholipid synthesis, including the phosphoinositides available for signal transduction at central nervous system level.

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

Cited by 45 publications

References 34 publications

Effects of L‐alpha‐glycerylphosphorylcholine on the EEG power spectrum in the rat

Effects of L‐alpha‐glycerylphosphorylcholine on the EEG power spectrum in the rat

Effects of chronic treatment with L‐alpha‐glycerylphosphorylcholine on hippocampal cholinergic transmission in the rat

Chronic L‐α‐Glyceryl‐phosphoryl‐choline Increases Inositol Phosphate Formation in Brain Slices and Neuronal Cultures

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