Rihlokain - anticonvulsant pharmacological tool

 

The invention relates to medicine, to use rihanana as anti-convulsants, excelling activity reference drugs and does not cause allergic reactions. table 2.

The invention relates to the field of medicine, specifically, to the preparation of rihlokain, benzoic ether, 1-allyl-2,5-dimethylpiperidine-4 hydrochloride, which can find application in medical practice as anti-convulsants.

Proposed drug rihlokain possessing anticonvulsant activity, according to the breadth of therapeutic action superior to many reference of this group of drugs with low toxicity, non-toxic and allergic reactions, side effects and highly portable sick.

Analogues of rihanana on anticonvulsant action are drugs diazepam, carbamazepine, phenobarbital, chlordiazepoxide, primidone. However, their application is limited due to severe side effects: changes in the blood, the emergence of mental disorders, allergic reactions, etc. (M. D. Mashkovsky. Medicinal product. - Vilnius, 1994, T. 1, page 24, 61-63).

The closest (prototype) to rhipiphoridae, possessing antiarrhythmic, local anesthetic, antinecrotic and anticonvulsant activity (USSR author's certificate 18234441, CL 07 D 211/48, a 61 K 31/445, 1990).

It has a pronounced anticonvulsant action is superior to phenobarbital in terms of maximal electroshock 9.1 times, comparable with phenobarbital in terms Karasyova seizures. However, the breadth of therapeutic action he is behind many of the reference drugs. This compound is toxic in comparison with relocaion 2 times.

The objective of the invention is to expand the Arsenal of anticonvulsants.

The technical result is achieved by the fact that the proposed drug rihlokain as anticonvulsant pharmacological tools.

Rihlokain - benzoic ester of 1-allyl-2,5-dimethylpiperidine-4 hydrochloride chemical formula:Rihlokain is a white or white to slightly yellowish crystalline powder, odorless, soluble in water, isotonic sodium chloride solution. In solutions of the drug is very strong, does not lose its activity during long-term storage (over 10 years), sterilized for 30 min in an autoclave at 120o

Rihlokain as usual means registered in the Republic of Kazakhstan (RK 5-000860) and the Russian Federation ( 95/250/2 and 95/250/8) included in the State register of drugs permitted for medical use and industrial production.

The invention is illustrated by the following examples: Determination of acute toxicity (median lethal dose LD substances). 0.5% solution intravenously, conducted experiments on awake white mice intraperitoneally on rabbits, rats and anesthetized with atenalol sodium 40 mg/kg cats (1. C. B. Prozorovsky. Using the method of least squares for probit analysis of the mortality curves // Pharmacology and toxicology. - 1962. , 25, 1. - S. 115-119. 2. C. B. Prozorovskii, M. P. Prozorovskaya. Tabular method for determining ED. LD substances with low biological activity // Pharmacology and toxicol. - 1980, - so-43, 6. - S. 733-735).

Indicators of toxicity LD in rats, rabbits, cats when administered intravenously are shown in table 1.

Anticonvulsant activity (PSA) of rihanana and comparative drugs (phenobarbital, hlordiazepoksida, carbamazepine, diazepam) was studied using maximal electroshock and Karasyova seizures. The data are shown in table 2.

In experiments using Karasyova seizures of rihlokain 2.2; 4,8 and 15.0 times on the DOG phenobarbital, carbamazepine and primidone, however, 5.0 and 2.3 times lower than the diazepam and hlordiazepoksida respectively. When taking into account the LD rihlokain 5.5; of 3.8 and 6.4 times has a great STD than phenobarbital, carbamazepine and primidone, however 6.9 and 1.6 times inferior in this respect to diazepam and hlordiazepoksida and accounting TD 8.3; 23,4; 92,6; 5.3 and 9.4 times that of phenobarbital, chlordiazepoxide, carbamazepine, diazepam and primidone.

For DOG and STD in experiments on mice of rihlokain and Comparators anticellulite can be placed in the following range: maximum electroshock - rihlokain > diazepam > carbamazepine > phenobarbital > chlordiazepoxide > primidone, STD: DT50/ED50- rihlokain > phenobarbital > primidone > carbamazepine = diazepam > chlordiazepoxide, LD50/ED50- rihlokain > diazepam > carbamazepine > chlordiazepoxide > phenobarbital > primidone; y is one, STD:DT50/ED50- rihlokain > diazepam > primidone = phenobarbital > chlordiazepoxide > carbamazepine, LD50/ED50diazepam > chlordiazepoxide > rihlokain > carbamazepine > phenobarbital > primidone.

Thus, rihlokain has a strong anticonvulsant effect in terms of maximal electroshock and Karasyova seizures. On the first model (Grand Mal seizures) is superior to PSA and STD phenobarbital, chlordiazepoxide, carbamazepine, diazepam and primidone, on the second (small seizures) - shows more pronounced anticonvulsant properties than phenobarbital, carbamazepine and primidone, however, inferior to the diazepam and hlordiazepoksida, has a large STD compared with phenobarbital, carbamazepine and geksamidinom inferior to diazepam and hlordiazepoksida.

Thus, the claimed drug anticonvulsant activity exceeds the reference drugs, does not cause allergic and toxic reactions, good move, for many indicators and therapeutic properties superior to known drugs of similar action and may find application in medical practice.

The formula image

as anticonvulsant pharmacological tools.

 

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14 cl, 36 ex

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