Combinations of Serotonin Reuptake Inhibitors and Imidazoline I 2 Agonists

Abstract

The present invention relates to combinations of serotonin reuptake inhibitors and imidazoline I2 agonists as separate chemical units or both properties combined in a single molecule and to the use thereof for the preparation of medicaments for the treatment of depression, obsessive-compulsive disorders (OCDs), obsessive-compulsive spectrum disorders (OCSDs) and other anxiety states.

Description

EXAMPLE A1

Injection Vials

A solution of 100 g of a substance and/or substance mixture according to the invention and 5 g of disodium hydrogenphosphate in 3 l of bidistilled water is adjusted to pH 6.5 using 2 N hydrochloric acid, sterile filtered, transferred into injection vials, lyophilised and sealed under sterile conditions. Each injection vial contains 5 mg of substance mixture.

EXAMPLE A2

Suppositories

A mixture of 20 g of a substance and/or substance mixture according to the invention is melted with 100 g of soya lecithin and 1400 g of cocoa butter, poured into moulds and allowed to cool. Each suppository contains 20 mg of substance mixture.

EXAMPLE A3

Solution

A solution is prepared from 1 g of a substance and/or substance mixture according to the invention, 9.38 g of NaH₂PO₄×2 H₂O, 28.48 g of NaH₂PO₄×12 H₂O and 0.1 g of benzalkonium chloride in 940 ml of bidistilled water. The pH is adjusted to 6.8, and the solution is made up to 1 l and sterilised by irradiation. This solution can be used in the form of eye drops.

EXAMPLE A4

Ointment

500 mg of a substance and/or substance mixture according to the invention are mixed with 99.5 g of Vaseline under aseptic conditions.

EXAMPLE A5

Tablets

A mixture of 1 kg of a substance and/or substance mixture according to the invention, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is pressed to give tablets in a conventional manner in such a way that each tablet contains 10 mg of substance mixture.

EXAMPLE A6

Dragees

Tablets are pressed analogously to Example E and subsequently coated in a conventional manner with a coating of sucrose, potato starch, talc, tragacanth and dye.

EXAMPLE A7

Capsules

2 kg of a substance and/or substance mixture according to the invention are introduced into hard gelatine capsules in a conventional manner in such a way that each capsule contains 20 mg of the substance mixture.

EXAMPLE A8

Ampoules

A solution of 1 kg of a substance and/or substance mixture according to the invention in 60 l of bidistilled water is transferred into ampoules, lyophilised under sterile conditions and sealed under aseptic conditions. Each ampoule contains 10 mg of substance mixture.

Claims

1. Substance which inhibits serotonin reuptake and at the same time binds agonistically to the imidazoline I2 receptor and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios.

2. Substance mixture comprising one or more compounds from the group of the serotonin reuptake inhibitors (SRIs) and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios, and one or more compounds from the group of the imidazoline I2 agonists and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios.

3. Substance mixture according to claim 2, comprising fluoxetine and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios, and one or more compounds from the group of the imidazoline I2 agonists and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios.

4. Substance mixture according to claim 2, comprising one or more compounds from the group of the serotonin reuptake inhibitors (SRIs) and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios, and 2-(2-benzofuranyl)-2-imidazoline (2-BFI) and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios.

5. Substance mixture according to claim 2, comprising fluoxetine and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios, and 2-BFI and/or solvates, stereoisomers and pharmaceutically usable derivatives thereof, including mixtures thereof in all ratios.

6. Substance or substance mixture according to claim 1 as medicament.

7. Pharmaceutical composition, characterised by a content of a substance or substance mixture according to claim 1 and optionally excipients and/or adjuvants.

8. Use of a substance or substance mixture according to claim 1 for the preparation of a medicament for the treatment or prophylaxis of diseases in which the inhibition of serotonin reuptake and the agonistic binding to the imidazoline I2 receptor results in improvement of the clinical picture.

9. Use according to claim 8, characterised in that the diseases are depression, obsessive-compulsive disorders (OCDs), obsessive-compulsive spectrum disorders (OCSDs) and other anxiety states.