DK164310B - N-(2-Aminoethyl)pyridine-2-carboxamide, and pharmaceutically utilizable acid addition salts thereof, for use as therapeutically effective substances, and medicaments which comprise these compounds - Google Patents

Description

DK 164310 B

in

The present invention relates to the compound N- (2-aminoethyl) -pyridine-2-carboxamide and its pharmaceutically acceptable acid addition salts for use as therapeutically active agents, especially as antidepressants or anti-Parkinson agents.

Surprisingly, it has been found that, with low toxicity, this compound and its acid addition salts have interesting and therapeutically useful pharmacodynamic properties.

In animal experiments, it has been shown that the above 10 compounds have monoamine oxidase (MAO) inhibitory properties.

The present invention further relates to medicaments containing the above compound or a pharmaceutically useful acid addition salt thereof, together with a therapeutically inert additive, these drugs being useful in the control or prevention of diseases or in improving health, especially in the control or prevention of depressive disorders. conditions and parkinsonism.

In Acta Polon. Pharm., 39, 41 (1982), the compound N- (2-aminoethyl) -pyridine-2-carboxamide is disclosed without indication of any biological effect.

The term "pharmaceutically useful acid addition salts" includes salts of red inorganic and organic acids, e.g. hydrochloric, hydrobromic, nitric, sulfuric, phosphoric, citric, formic, maleic, acetic, succinic, tartaric, methanesulfonic and p-toluenesulfonic acids. Such salts can be readily prepared by any skilled person for the state of the art and for the nature of the compound to be converted to a salt.

The above compound and its pharmaceutically useful acid addition salts have - as already mentioned above - monoamine oxidase (MAO) inhibitory activity. Because of this activity, these compounds can be used to treat depressive conditions and parkinsonism.

The MAO inhibitory activity of the subject compound, N- (2-aminoethyl) -pyridine-2-carboxamide, may be

DK 164310 B

is voted using standard methods. Thus, rats are administered the test preparation p.o. Two hours later, the animals are killed and the MAO-inhibitory activity is measured in homogenates of the brain according to that in Biochem. Pharmacol. 12, 1439-1441 5 (1963), but using phenethylamine (2 * 10 "5 mol * l-1) instead of tyramine as a substrate.

For the above-mentioned compound in the form of the dihydrochloride, an ED 50 value of 1.7 μιηοΐ is obtained. kg (p.o. for rats) and an LD50 value of> 4000 mg per day. kg (p.o. for mice).

The present compound and its pharmaceutically useful acid addition salts can be used as drugs, e.g. in the form of pharmaceutical preparations. The pharmaceutical compositions may be used orally, e.g. in the form of tablets, lacquer tablets, dragees, hard and soft gelatin capsules, solutions, emulsions or suspensions. However, the application can also be done rectally, e.g. in the form of suppositories, or parenterally, e.g. in the form of injection solutions.

For the preparation of tablets, lacquer tablets, dragees and hard gelatin capsules, the above compound or a pharmaceutically usable acid addition salt thereof can be processed with pharmaceutically inert, inorganic or organic additives. As such additives, e.g. lactose, corn starch or derivatives thereof, talc, stearic acid or the salts thereof are used for tablets, dragees and hard gelatin capsules.

For soft gelatin capsules, e.g. vegetable oils, waxes, fats and semi-solid and liquid polyols suitable as additives.

For the preparation of solutions and syrups, e.g.

30 water, polyols, sucrose, invert sugar and glucose suitable as additives.

For injection solutions, e.g. water, alcohols, polyols, glycerol and vegetable oils suitable as additives.

35 For suppositories, e.g. natural or hardened oils, waxes, fats, semi-liquid or liquid 3

DK 164310 B

polyols suitable as additives.

In addition, the pharmaceutical compositions may also contain preservatives, solvents, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, aromatizers, salts for altering the osmotic pressure, buffering agents, coating agents or antioxidants. The compositions may also contain other therapeutically valuable compounds.

The present compound as well as its pharmaceutically useful acid addition salts can be used to control or prevent depressive conditions and parkinsonism. The dosage can be varied within wide limits and must, of course, in each case be adapted to the individual given conditions. In general, a daily dose of about 15 10 to approx. 100 mg of one of these compounds by oral administration may be appropriate, however, the above-mentioned upper limit may also be exceeded if this proves to be appropriate.

The present invention is explained in more detail in the following examples.

EXAMPLE A

Gelatine capsules and 5 more

Composition 25 1. N- (2-aminoethyl) pyridine-2-carboxamide dihydrochloride 5.75 mg *) 2. Milk sugar, powder. 80.25 mg 3. Corn starch 40.00 mg 4. Talk 3.60 mg 30 5. Magnesium stearate 0.40 mg 6. Milk sugar, cryst. 110.00 mg

Capsule filling weight 240.00 mg

Preparation method: 35 1-5 are mixed and sieved through a sieve with a mesh width of 0.5 mm. Then add 6 and mix. This 4

DK 164310 B

Fill-ready mixture is filled into gelatin-sized capsules of a suitable size (eg # 2) and with a single fill weight of 240 mg.

5 1) corresponds to 5 mg base

EXAMPLE · B

Tablets and 5 mg

Composition 10 1. N- (2-aminoethyl) -pyridine-2-carboxamide dihydrochloride 5.75 mg 1) 2. Milk sugar, powder. 104.25 mg 3. Corn starch 45.00 mg 4. Polyvinylpyrrolidone K 30 15.00 mg 15 5. Corn starch 25.00 mg 6. Talc 4.50 mg 7. Magnesium stearate 0.50 mg

Tablet Weight 200.00 mg 20 Processes 1-3 are mixed and sieved through a sieve with a mesh width of 0.5 mm. This powder mixture is wetted with an alcoholic solution of 4 and kneaded. The moist mass is granulated, dried and processed to a suitable grain size. 5, 6 and 7 are added successively to the dried granules and mixed.

The ready-made mixture is pressed into tablets of an appropriate size with a calculated weight of 200 mg.

corresponds to 5 mg base 5

DK 164310 B

EXAMPLE C

Gelatin capsules to 10 mg

Composition: 1. N- (2-aminoethyl) -pyridine 5 -2-carboxamide dihydrochloride 11.82 mg *) 2. Milk sugar, powder. 74.18 mg 3. Corn starch 40.00 mg 4. Talk 3.60 mg 5. Magnesium stearate 0.40 mg 10 6. Milk sugar, cryst. 110.00 mg

Capsule filling weight 240.00 mg

Preparation Method: Mix 1-5 and screen through a sieve with a mesh width of 0.5 mm. Then add 6 and mix. This pre-filled mixture is filled into gelatin-sized capsules of a suitable size (eg, No. 2) and with a single fill weight of 240 mg.

20 *) equals 10 mg base.

EXAMPLE D

Tablets to 10 mg

Composition 25 1. N- (2-aminoethyl) pyridine-2-carboxamide dihydrochloride 11.82 mg *) 2. Milk sugar, powder. 103.18 mg 3. Corn starch 40.00 mg 4. Polyvinylpyrrolidone K 30 15.00 mg 30 5. Corn starch 25.00 mg 6. Talk 4.50 mg 7. Magnesium stearate 0.50 mg

Tablet weight 200.00 mg

DK 164310 B

6

Procedure: 1-3 mix and sieve through a sieve with a mesh width of 0.5 mm. This powder mixture is wetted with an alcoholic solution of 4 and kneaded. The moist mass is granulated, dried and processed to a suitable grain size. 5, 6 and 7 are successively added to the dried granules and mixed.

The ready-made mixture is pressed into tablets of an appropriate size with a calculated weight of 200 mg.

10 *) equals 10 mg base.

Claims (2)

1. N- (2-Aminoethyl) -pyridine-2-carboxamide and the pharmaceutically useful acid addition salts of this compound for use as therapeutically active agents, especially as antidepressants or anti-Parkinson agents. Drug, especially antidepressant or anti-Parkinson's, characterized in that it contains N- (2-aminoethyl) pyridine-2-carboxaride or a pharmaceutically useful acid addition salt thereof and a therapeutically inert additive.