Absorption, tissue distribution and excretion of radiolabelled compounds in rats after administration of [14C]-l-α-glycerylphosphorylcholine

Abstract

The kinetics and metabolism of L-alpha-glycerylphosphoryl-choline (alpha-GPC) were investigated in male and female rats after i.v. (10 mg/kg) and oral doses (100-300 mg/kg). alpha-GPC was labelled with [14C]-glycerol ([14G]-GPC) or [14C]-choline ([14C]-GPC). Different kinetic and metabolic profiles were observed after i.v. and oral administration. It is assumed that alpha-GPC is hydrolyzed by phosphodiesterases in the gut mucosa. The different labelled metabolites have different kinetic properties of absorption, distribution and clearance, leading to different blood concentration-time curves of total radioactivity. Both labelled compounds gave a wide distribution of radioactivity, particularly concentrated in the liver, kidney, lung and spleen compared to blood. Brain concentrations of [14C]-GPC were comparable to ([14G]-GPC) or lower than ([14C]-GPC) total blood radioactivity. The metabolite profile in the perfused brain showed a small amount of choline and two unknown metabolites, probably the same as in blood. In addition, choline was incorporated into brain phospholipids in increasing amounts within 24 h of dosing. In all cases renal and fecal excretion of radioactivity was low and comparable for [14G]-GPC and [14C]-GPC. Mostly the administered radioactivity was exhaled as 14CO2, this degradation being faster and more pronounced for the glycerol-labelled metabolites than for the choline-labelled metabolites for both routes of administration. In all cases the results were the same for male and female rats.

Cholinergic precursors in the treatment of cognitive impairment of vascular origin: Ineffective approaches or need for re-evaluation?

“…choline precursors and is incorporated into brain phospholipids within 24 h from absorption [35]. Preclinical studies, have documented that choline alphoscerate increases the release of acetylcholine in rat hippocampus, facilitates learning and memory, counters cognitive deficit in experimental models of aging brain and reverses memory deficits induced by scopolamine administration (see [23]).…”

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

“…The molecular mechanisms underlying CDP-choline-induced cognitive enhancement are still unclear, but one possibility is that CDP-choline counters the progression of ischemic damage by reducing the release of free fatty acids [44] . Choline alphoscerate, a semi-synthetic derivative of lecithin that does not carry the electrical charge of endogenous choline, can be incorporated into brain phospholipids within 24 h of absorption, resulting in a more rapid increase in free plasma choline than other uncharged choline precursors [54] . Preclinical studies have demonstrated that choline alphoscerate increases the release of ACh in the rat hippocampus and facilitates learning and memory in animal models of aging [55] .…”

Effect of choline-containing phospholipids on brain cholinergic transporters in the rat

“…Both are natural, water-soluble compounds providing comparable effects in different conditions [11]. After oral administration, both CDP-choline and choline alphoscerate have been shown to cross the blood-brain barrier and reach the central nervous system, where they are incorporated into the phospholipid fraction of the neuronal plasma membrane and in microsomes [12,13].…”