Pyritinol and Phosphatidylserine
Ann. New York Acad. Sci. (USA) , 1993, 695/- (327-331)
Forty patients with probable Alzheimer's disease were selected from a pool of 80 patients and assigned to four groups. Each received either social support, cognitive training only, or cognitive training in combination with pyritinol or phosphatidylserine. Treatment duration was 6 months. Before and after treatment the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography (PET) and 2(18F)-fluoro-2-deoxy-D-glucose (FDG). Before treatment, the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. They did not differ in scores of a neuropsychological test battery. After the treatment period the group with cognitive training plus phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions, and an improvement in cognitive functioning compared to other groups. The group with cognitive training plus pyritinol had better stimulation effect than that of the social support group, indicating that a combination of cognitive training and pharmacological intervention was superior than that of cognitive training alone.
Phospholipid in Parkinson's disease: Biochemical and clinical data
ITALY PROG. CLIN. BIOL. RES. (USA), 1980, VOL.39 (205-214)
Phosphatidylserine administration stimulates TH activity in rat brain tissues, and this effect is paralleled by modification of other factors involved in dopaminergic transmission in the striatum and in the hypothalamic-pituitary axis. A phospholipid mixture in which PS is assumed to be the active component improves the classic symptomatology which characterizes Parkinson's disease, partially but with statistical significance. This effect is accompanied by modification in normal subjects of cerebrospinal fluid HVA and serum growth hormone and prolactin level. We do not know if the improvement observed in Parkinson's disease symptomatology upon BC-PL treatment is related to the biochemical changes previously observed in human beings and to the pharmacological and clinical effects reported with other phospholipid preparations causing modification of catecholamine synthesis in rat brain. The molecular mechanism by which administered phospholipids achieve the reported effect is still under investigation, to establish (i) whether it reflects liposome penetration into brain fluids and (ii) whether the conversion of diacyl-phospholipids into some active metabolite(s) is necessary for obtaining the results.
Effects of phosphatidylserine in Alzheimer's disease.
Psychopharmacol Bull (UNITED STATES) 1992, 28 (1) p61-6
We studied 51 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients were treated for 12 weeks with a formulation of bovine cortex phosphatidylserine (BC-PS; 100 mg t.i.d.) or placebo, and those treated with the drug improved on several cognitive measures relative to those administered placebo. Differences between treatment groups were most apparent among patients with less severe cognitive impairment. Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD.
Nootropic drugs and brain cholinergic mechanisms.
Prog Neuropsychopharmacol Biol Psychiatry (ENGLAND) 1989, 13 Suppl pS77-88
Direct or indirect evidences indicating an activation of cholinergic mechanisms exist for pyrrolidinone derivatives including piracetam, oxiracetam, aniracetam, pyroglutamic acid, tenilsetam and pramiracetam and for miscellaneous chemical structures such as vinpocetine, naloxone, ebiratide and phosphatidylserine. All these drugs prevent or revert scopolamine- induced disruption of several learning and memory paradigms in animal and man. Phosphatidylserine restores acetylcholine synthesis and conditioned responses in aging rats. The mechanisms through which the action on cholinergic systems might take place, including stimulation of the high affinity choline uptake, are discussed.
Effects of phosphatidylserine in age-associated memory impairment.
Neurology (UNITED STATES) May 1991, 41 (5) p644-9
We treated 149 patients meeting criteria for age-associated memory impairment (AAMI) for 12 weeks with a formulation of phosphatidylserine (100 mg BC-PS tid) or placebo. Patients treated with the drug improved relative to those treated with placebo on performance tests related to learning and memory tasks of daily life. Analysis of clinical subgroups suggested that persons within the sample who performed at a relatively low level prior to treatment were most likely to respond to BC-PS. Within this subgroup, there was improvement on both computerized and standard neuropsychological performance tests, and also on clinical global ratings of improvement. The results suggest that the compound may be a promising candidate for treating memory loss in later life.
Effect of phosphatidylserine on the binding properties of glutamate receptors in brain sections from adult and neonatal rats.
Brain Res (NETHERLANDS) Nov 18 1996, 740 (1-2) p337-45
The effects of phosphatidylserine (PS) on the binding properties of the AMPA (alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) subtypes of glutamate receptors were analyzed by quantitative autoradiography of [3H]AMPA, [3H]6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) and [3H]glutamate binding on rat brain tissue sections. Preincubation of brain sections with PS produced an increase in [3H]AMPA binding without modifying the binding properties of [3H]CNQX, an antagonist of AMPA receptors. This effect of PS appeared to be specific for the AMPA subtype of glutamate receptors as the same treatment did not modify [3H]glutamate binding to the NMDA receptors. Furthermore, the PS-induced increase in [3H]AMPA binding was different in various brain structures, being larger in the molecular layer of the cerebellum and almost absent in the striatum. Preincubation with calcium also augmented [3H]AMPA binding, and the lack of additivity of the effects of calcium and PS on [3H]AMPA binding strongly suggests that both treatments share a common mechanism(s) for producing increased agonist binding. Finally, the effect of PS on AMPA receptor properties was markedly reduced in rat brain sections prepared from neonatal rats at a developmental stage that is normally characterized by the absence of LTP expression in certain brain regions. The present data are consistent with the hypothesis that alteration in the lipid composition of synaptic membranes may be an important mechanism for regulating AMPA receptor properties, which could be involved in producing long-lasting changes in synaptic operation.
Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents.
J Nutr Sci Vitaminol (Tokyo) (JAPAN) Feb 1996, 42 (1) p47-54
Soybean transphosphatidylated phosphatidylserine (SB-tPS) was prepared from soybean phosphatidylcholine by transphosphatidylation using phospholipase D, and the fatty acids composition and pharmacological properties were compared with those of bovine brain cortex-derived phosphatidylserine (BC-PS) which was reported to improve cognitive disorders of senile dementia patients by oral administration (300 mg/day). The molecular species of SB-tPS are rich in linoleic and palmitic acids whereas those of BC-PS are stearic and oleic acids. Despite the differences in fatty acid composition, SB-tPS displayed significant activities on the increase in brain glucose concentrations in mice (79 mg/kg, i.v.) and the restoration of scopolamine-induced amnesia in rats (60 mg/kg, i.p.) as did BC-PS. These results suggest the possibility that SB-tPS may prevent and/or improve senile dementia by oral administration.
Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation
DEMENTIA (Switzerland), 1994, 5/2 (88-98)
70 patients with probable Alzheimer's disease were randomly allocated to four groups: 17 patients received only social support. 18 cognitive training twice a week, in 17 cognitive training was combined with pyritinol 2 x 600 mg/day and in 18 cognitive training was combined with phosphatidylserine 2 x 200 mg/day. Treatment duration was 6 months. Before and after treatment, the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose. Before treatment the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. Electrophysiological changes were assessed as EEG power, globally and in 4 frequency bands. This 6-month study in four groups of patients with Alzheimer's disease indicated that phosphatidylserine treatment has an effect on different measures of brain function. Since neuropsychological improvements were best documented after 8 and 16 weeks and faded towards the end of the treatment period, it must be concluded that this symptomatic therapy is mainly of short-term benefit and was overcome by the progressive pathological changes at the end of the treatment period.
Advances in the pharmacotherapy of Alzheimer's disease
EUR. ARCH. PSYCHIATRY CLIN. NEUROSCI. (Germany), 1994, 244/5 (261-271)
The authors reviewed the literature on the agents proposed for the treatment of Alzheimer's disease (AD). Different classes of drugs have been tested for this indication including psychostimulants, anticoagulants, vasodilators, hyperbaric oxygen, hormones, nootropics, cholinomimetics, monoaminergics and neuropeptides without conclusive evidence of being beneficial for the treatment of this condition. Among the cholinomimetics recent research data seems to indicate that they might produce modest benefits in mild-to-moderate AD patients. Recently, other drugs have also been proposed including neurotrophic factors, phosphatidylserine, argistension converting enzyme (ACE) inhibitors, calcium channel blockers, acetyl-L-carnitine, xanthine derivatives, anti-inflammatory agents, aluminum chelate agents, and D-cycloserine. Of these new strategies few hold promise of more substantial benefits for AD, with the possibility of altering the course of the disease, but these drugs await confirmatory trials.