Glycyl-p-amino-pyridine for the treatment of senile dementia sta

Details Glycyl-p-amino-pyridine for the treatment of senile dementia sta Glycyl-p-amino-pyridine for the treatment of senile dementia sta

1992-06-02

1993-09-14

Friedman, S. J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

A61K 31505

Patent

active

052448975

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to the use of glycyl-p-amino-pyridine monoacetate of formula I ##STR1## to prepare a medicament, which is particularly useful in the treatment of psychic and physical fatigue syndromes, memory disturbances, senile deficiency, psychoinvolution, nervous breakdown, and the like.
The present compound, hereinafter named with the code MR-3066, was disclosed in Indian Journal of Chemistry 5/524 1967 and in El. Naggar et al. J.Sci.Res.1986 4 (2) (473/83 pag); in this last paper the antibacterial, disinfectant and antiseptic properties of various amino-acyl-amino-pyridines and amino-acyl-amino-pyrimidines are described.
It has now been found that the compound MR-3066 is endowed with anticonvulsivant properties, with effects on the cerebral acetylcholine release (without nevertheless showing Parkinson-like effect), with positive influence on learning and on amnesia episodes.
Therefore, the compound MR-3066 can be advantageously used in neurologic medicine for the treatment of symptoms and syndromes such as, for instance, the Alzheimer's disease (or senile dementia), for which no specific drugs exist so far. Aminopyridines affect the neurotransmitter release, by increasing it (Paskow et al., 1986) and at high dosages they induce convulsions.
Aminopyridines have been tested with favourable results in several clinical conditions ranging from diseases of neuromuscular transmission, including multiple sclerosis (Stefoski et al., 1987), to recovery from anaesthesia (Lechat et al., 1982; Pascow et al., 1986).
In Alzheimer's disease, the patient's cerebral cortex is remarkably damaged owing to neurohistological variations (neurofibrillar variations, etc), generally against temporal and frontal lobes, with resulting intellectual function deterioration; the initial clinical picture appears with psychogenic disorders, anxiety and depression, followed by confusion, memory disorders, reduced comprehension and judgement capacity, until to a total patient absence.
At the moment there is no effective therapy to treat this disease, which is considered to be irreversible.
The seriousness of the disease and its social impact justify clinical trials of rather toxic compounds, such as aminopyridines.
It has been pointed out the remarkable activity of the compound, if not for the resolution, at least for decreasing the syndrome.


TOXICOLOGIC AND PHARMACOLOGICAL EVALUATIONS



1) Acute toxicity

The acute toxicity of MR-3066 was evaluated after oral administration of the drug to the Swiss mice versus 4-aminopyridine.
The LD.sub.50 was calculated according to the method described by Litchfield and Wilcoxon (J. Pharmacol. Exp. Ther. 96, 99; 1949).


TABLE 1 ______________________________________ Results Drug LD.sub.50 (mg/kg os) ______________________________________ MR-3066 29 4-aminopyridine 12 ______________________________________
The symptoms preceeding death were agitation, aggressiveness, jerks, stretchings and tonic convulsions.
MR-3066 showed a toxicity lower than 4-aminopiridine.


Acute convulsant activity

The acute convulsant activity of MR-3066 and 4-aminopyridine was compared in Swiss male mice after oral administration
The CD.sub.50 (Convulsant Doses 50) were calculated according to the method described by Litchfield and Wilcoxon (J. Pharmacol. Exp. Ther. 96, 99; 1949).


TABLE 2 ______________________________________ Results Drug CD.sub.50 (mg/kg os) ______________________________________ MR-3066 19 4-aminopyridine 5 ______________________________________
MR-3066 resulted less convulsant than 4-aminopyridine.


Toxicity after repeated administration--Preliminary study

The toxicity of MR-3066 after repeated administration was evaluated in male and female Sprague Dawley rat after oral administration of the drug (6 mg/kg) for 30 consecutive days.


Results

The oral administration of MR-3066 for 30 days to the rat brought no toxic phenomenon except for a slight decrease in body weight, increase in the female accompanied by a reduction in food consumption.
No sign

Affiliated with

Also associated with

Rating

Glycyl-p-amino-pyridine for the treatment of senile dementia sta does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Glycyl-p-amino-pyridine for the treatment of senile dementia sta, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Glycyl-p-amino-pyridine for the treatment of senile dementia sta will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2026710