PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CEREBRAL PSYCHO-ORGANIC SYNDROMES

Abstract: Pharmaceutical compositions containing as the active principle L- alpha -glycerylphosphorylcolamine (L- alpha -glycerylphosphorylethanolamine or GPE), for the treatment of chronic cerebral psycho-organic syndrome of involutive kind or due to cerebrovascular insufficiency as well as of symptomatology related therewith.

Description: PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CEREBRA 'Λ PSYCHO-ORGANIC SYNDROMES The invention refers to pharmaceutical compositions containing as the active principle L- Λ -glyceryl- phosphorylcolamine for the treatment of cerebral psycho-organic syndromes. 5 The L- Λ-glycerylphosphorylcolamine or L-Λ- glycerylphosphorylethanolamine (GPE) (J. Am. Chem. Soc. 75, 4510-14, 1953), physiological metabolite in the lipids metabolism, is a deacylated precursor of cephalins, part¬ icularly abundant phospholipids in the central nervous 10 system. * The L- Λ -glycerylphosphorylcolamine is also a precursor of glycerylphosphorylcholine and of phosphat- idylcholine. According to what is presently known on the cere- 15 bral metabolism and biochemistry it is however impossible to devise any therapeutic use for GPE. It has now been surprisingly found that GPE, administered to laboratory animals is able to significant¬ ly improve the response to the learning and memory tests, 20 whereas, when administered to man, it has shown the ability to influence in a likewise significant way the neurophysiological parameters, the psychometric tests and the used neurologic scales. Said pharmacological actions are probably due on 25 one side to the activation of the phospholipidε biosyn¬ thesis in the microsomes of the Central Nervous System (CNS) and on the other to the stimulation of the biosynthesis of the neurotransmitter acetylcholine, through the metabolic intermediates glycerylphoεphorylcho- line and phosphatidylcholine. It is well known .in fact that the fxequent memory disturbances constantly found in aging are related with a 5 decrease of the central cholinergic transmission: it has been shown in fact that a functional and anatomic impairment of cholinergic circuits constantly accompanies the alteration of the mnemonic functions (Drachman D.A., Sahakiam B.J. : Effects of cholinergic agents on human 10 learning and memory, in: Nutrition and brain, 5, Barbeau A. et al. J. edε. 351-361, Raven Press Pubs, New York, 1979) . The validity of "the invention is not in any way connected to the verification of the above stated 15 mechanisms of action. The results obtained with GPE in pharmacological and clinical tests are reported hereinafter. TOXICITY It is meaningless to speak of subacute or chronic 20 toxicity " fox GPE, which is a physiological metabolite normally present in the human body. As far as acute toxicity is concerned, the follow¬ ing data are obtained: Oral route up to 3 g/kg did not cause either death or "25 any symptomatology both in mice and rats and in rabbits. Intramuscular route LD - in mice and rats > 1500 mg/kg in rabbits > 1000 mg/kg. PHARMACOLOGICAL TESTS " 30 - The GPE administered "i.p. to 20 male mice at the dose of 100 mg/kg subjected to the electroshock test as described by Eεεeman in Pharmacol. Res. comm. j>, 295-302 1973, and at the same dose and for the same route to 2 male rats subjected to the pole-climbing test as describe by Cook and eindley (Ann. N.Y. Acad. Sci. 66, 740-752 5 1957) has significantly shown the ability to activat learning and memory in comparison to the untreate animals. CLINICAL TESTS The above described pharmacological activity ha 0 been confirmed in clinical tests in the treatment o senile cerebral alteration, of both involutive an cerebro-vascular insufficiency origin, and of the relate symptomatology, such as slowing of psychic activity, memory and alertness decrease, mood alteration, emotiona weakness, irascibility, anxiety, etc. 20 patients (10 male and 10 female) 59 to 76 year old were treated; the overall clinical evaluation, takin into account the improvement of the neurophysiological an neurological exams carried out, of the psychometric tests and of the used neurological scale (De Renzi E., Nichelli P.: Verbal and non-verbal short-term memory impairment following hemispheric damage, Cortex, 11, 341-354, 1975; Bisiach E. et. al. : Neurologia Clinica, Ricerche di pεicologia, Ed. F. Angeli, Milano, 1977; Cafarra P. et al. : Neuropsychological testing during a transient global amnesia episode and its follow-up, Acta Neurol. Scand. 63, 44-50, 1981; Kobs S.C.: Intelligence measurement, Mc Milan Pubs, New York, 1923), has shown a significantly positive therapeutic effect in 19 cases, whilst only one treatment was considered to be insufficient. The tolerability was always excellent. The results are reported in the table. From what reported above, it is evident how GPE ca a be conveniently used in the therapy of chronic cerebra j j psycho-organic syndromes both of involutive kind an caused by cerebrovascular insufficiency and in th 5 treatment of the symptomatology related therewith (poo attention and concentration ability, mental confusion, loss of memory, anxiety, emotional weakness, depresse mood, alteration of alertness condition). For the considered therapeutic uses, GPE may b 10 administered as such or in form of suitable pharmaceutical composition, using conventional techniques and excipients such as those described in "Remington's Pharmaceutical Sciences Handbook", Hack Pub. Co. New York, USA. The preferred administration routes are the oral 15 route and the parenteral route. Examples of suitable pharmaceutical compositions comprise therefore capsules, tablets, solutions, syrups, sachets, vials. The daily posology will depend on several factors 20 such as the seriousness of the disease to be treated, patient's weight, age and sex, response to the treatment etc. It will generally range from 0,5 to 3 g daily, optionally divided in more administrations. Higher doses are not however contraindicated. 25 The following examples illustrate and do not limit the invention. EXAMPLE 1 Tablets τπg 250 mg 500 5 GPE mg 250 mg 500 Lactose mg 100 mg 200 • . Starch „ mg -75 mg 150 Talc mg 20 mg 40 Microcrys. cellulose mg 50 mg 100 0 Magnesium stearate mg 2 mg 4 ^EXAMPLE 2 Buvable vials 5 GPE mg 1.000 Sodium saccharinate mg 15 Glycerol mg 100 Flavour mg 20 .Purified water q.b. to mg 10 0 EXAMPLE 3 Lyophylized vials mg 250 mg 1.000 5 GPE -mg 250 mg 1.000

Claims: CLAIMS 1. L- rt.-glycerylphoεphorylcola ine as therapeutic agent. 2. Pharmaceutical composition for the treatment of chronic cerebral psycho-organic syndrome of involutive kind or due to cerebrovascular insufficiency containing as the active principle L- Λ -glycerylphoεphorylcolamine in admixture with suitable pharmaceutical carriers. 3. Compositions according to claim 2, contaihing unit doses of active principles from 250 to 1.000 m . 4. Compositions according to claims 2 or 3, in form of capsules, tablets, solutions, vials, syrups, sachets. 5. Use of L- Λ -glycerylphosphorylcolamine for the preparation of a drug for the therapy of chronic cerebral psycho-organic syndrome of involutive kind or due to cere¬ brovascular insufficiency.

Inventors: LODI ROSANNA, LODI, ROSANNA
Applicants: RIACE ETS, RIACE ESTABLISHMENT
Application year: 1988
Main classification: A61K31
IPC codes: A61K31, A61P25