Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-06-06
1997-10-07
Jarvis, William R.A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 31425
Patent
active
056748850
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This application claims priority to PCT/FR94/00003 filed Jan. 3, 1994.
The present invention relates to a novel therapeutic application of riluzole (6-trifluoromethoxy-2-aminobenzothiazole) or the pharmaceutically acceptable salts of this compound.
BACKGROUND OF THE INVENTION
Riluzole is useful as an anticonvulsant, anxiolytic and hypnotic medicinal product (Patent EP 50,551), in the treatment of schizophrenia (EP 305,276), in the treatment of sleep disorders and depression (EP 305,277), in the treatment of cerebrovascular disorders and as an anaesthetic (EP 282,971).
DESCRIPTION OF THE INVENTION
It has now been found, surprisingly, that this compound may also be used in the treatment of Parkinson's disease and parkinsonian syndromes.
The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is known to induce a syndrome similar to Parkinson's disease. This syndrome results from a degeneration of the dopaminergic nigrostriatal neurons in primates (R. S. Burns et al., Proc. Natl. Acad. Sci., 80, 4546-4550 (1983)), in man (J. W. Langston et al., Science, 219, 979-980 (1983)) and in mice (R. E. Heikkila et al., Science, 224, 1451-1453 (1984)).
EXAMPLES
The activity of riluzole was hence demonstrated in mice by measuring MPTP-induced decreases in the striatal and cortical dopamine levels in comparison with those of control animals.
Mice (C57BL/6) weighing 20-25 g are injected intraperitoneally 3 times at 2-hour intervals with 15 mg/kg of MPTP. Thirty minutes before the first injection of MPTP, and then 2 hours 30 minutes, 5 hours 30 minutes and 7 hours 30 minutes after the first injection of MPTP, from 1 to 40 mg/kg of the product under study, depending on the product, are administered. Over the next 3 days, from 1 to 40 mg/kg of the product under study, depending on the product, are administered twice daily. The mice are sacrificed 8 days after injection of MPTP. The striatum and the frontal cortex are dissected and stored at -70.degree. C. until the time of their analysis. Dopamine levels are measured by high pressure liquid chromatography with electrochemical detection. Statistical analyses are performed using ANOVA followed by Scheffe's test.
The results obtained are recorded in the following table:
______________________________________ dopamine level
dopamine level pmol/mg
pmol/mg in the
in the frontal cortex
striatum (% relative
(% relative to
to controls)
controls)
______________________________________
controls 876 .+-. 64 2.486 .+-. 0.290
animals 219 .+-. 18 1.481 .+-. 0.180
receiving only
(-75%) (-40%)
MPTP
animals 378 .+-. 39 2.359 .+-. 0.185
treated with (-57%) (-5%)
riluzole
______________________________________
As pharmaceutically acceptable salts, the addition salts with inorganic acids, such as hydrochloride, sulphate, nitrate or phosphate, or organic acids, such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulphonate, isethionate, theophyllineacetate, salicylate, phenolphthalinate or methylenebis(.beta.-hydroxynaphthoate), or substitution derivatives of these derivatives, may be mentioned in particular.
The medicinal products consist at least of riluzole, in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is combined with any other pharmaceutically compatible product, which may be inert or physiologically active. The medicinal products according to the invention may be employed orally or parenterally.
As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, wafer capsules) or granules may be used. In these compositions, the active principle according to the invention is mixed with one or more inert diluents such as starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions can also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a colouring, a coating (d
REFERENCES:
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Boireau Alain
Doble Adam
Dubedat Pierre
Louvel Erik
Meunier Mireille
Jarvis William R.A.
Rhone-Poulenc Rorer S.A.
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