Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
  • A61K31/425—Thiazoles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/24—Antidepressants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• the present invention relates to an agent with antidepressant activity containing 2-amino-4,5,6,7-tetrahydro-6-propylamino-benzothizole, its (+) or (-) enantiomer, its pharmacologically acceptable acid addition salts and a conventional antidepressant.
• the combination of pramipexole with sertraline is of particular interest.
• Pramipexole - the (-) - 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzo-thiazole - is a dopamine - D3 / D2 agonist, the synthesis of which is described in European Patent 186
• Pramipexole is primarily known for the treatment of schizophrenia and especially for the treatment of Parkinson's.
• German patent application DE 3843 227 discloses that pramipexole lowers the prolactin serum level.
• German patent application DE 39 33 738 it is known from German patent application DE 39 33 738 to use pramipexole to lower high TSH levels.
• the transdermal application is disclosed in US Patent 5,112,842, and WO patent application PCT / EP93 / 03389 describes the use of pramipexole as an antidepressant.
• pramipexole, its (+) or (-) enantiomer or its pharmacologically acceptable acid addition salts in combination with a further antidepressant has a significantly higher antidepressant effect than the two individual components can do for themselves.
• the improved effect of pramipexole by simultaneous administration of another antidepressant was found in studies on rats which were given pramipexole and sertraline in the so-called "forced swimming test”. Details of this test method can be found, for example, in Willner, Psychopharmacology 83, 1-16 (1984) or Borsini and Meli, Psychopharmacology 94, 147-160 (1988).
• the Test performed as follows. The animals were divided into different groups, and each group received either saline, a therapeutically effective amount of pramipexole, a therapeutic amount of sertraline or a combination of the two antidepressants in each case in the same therapeutic amount as the animals, which received only one of the two active substances .
• Another antidepressant can be used in combination with pramipexole.
• This other antidepressant is preferably one of the following:
• combination is understood according to the invention as a combination of active ingredients of the two active ingredients in a formulation and also as a combination in the sense of individual formulations of the active ingredients which are used in a temporally related therapeutic measure.
• Orally administrable pharmaceutical formulations for pramipexole are known from the prior art and are e.g. available on the German or US market.
• the individual active ingredients can also be packaged separately as putty in the sense of a combination of packs of the individual medicaments.
• pramipexole and another antidepressant can be formulated analogously to the usual pharmaceutical preparations, usually together with a pharmaceutical carrier.
• a pharmaceutical carrier I.e. an effective dose of the individual components and, if appropriate, a pharmaceutical carrier are formulated as a tablet, dragee, capsule, wafer, powder, solution, suspension, emulsion, syrup, suppository, etc.
• the pharmaceutically effective dose per patient is between 0.01 and 10 mg, preferably between 0.08 and 5 mg.
• the therapeutically effective doses of the second antidepressant in the combination are given in the table below.
• the recommended dosage in individual cases can also be below the previously recommended individual dosage of the monopreparation.
• Pramipexole was used in doses of 0.1 and 0.3 mg / kg. In addition, tests with 0.05 mg / kg pramipexole were carried out. Sertraline was used in doses of 5 and 10 mg / kg as listed in the tables. The experiments were carried out on rats (male Wistar, 250-270 g) at RT while maintaining a natural day-night rhythm. Pramipexole (HCI) was dissolved in a physiological saline solution and sertraline (HCI) in distilled water, both substances were injected in a volume of 2 ml / kg.
• Pramipexole - 0.1 mg / kg - does not change the immobility time in the forced swimming test, while higher doses (0.3 mg) cause a significant reduction in the immobility time.
• a dose of 5 mg / kg sertraline alone does not reduce the immobility time either. But the combined application of 5 mg / kg sertraline and 0.1 mg / kg pramipexole noticeably reduce the immobility time. This effect is much more pronounced with higher doses of sertraline.
• Pramipexole (0.1 or 0.3 mg / kg s.c.) and sertraline (5 mg / kg i.p.) are administered 3 times (24.5 and 1 hour) before the test.
• Pramipexole (0.1 or 0.3 mg / kg sc) and sertraline (10 mg / kg ip) are administered 3 times (24.5 and 1 hour) before the test.
• Table 3 Effect of pramipexole (0.05 mg / kg) alone or in combination with sertraline (5 and 10 mg / kg) on immobility time in the forced swimming test in rats.
• Pramipexole (0.05 mg / kg s.c.) and sertraline (5 and 10 mg / kg i.p.) are administered 3 times (24.5 and 1 hour) before the test.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Organic Chemistry (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Neurosurgery (AREA)
• Neurology (AREA)
• Biomedical Technology (AREA)
• Pain & Pain Management (AREA)
• Psychiatry (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Thiazole And Isothizaole Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Priority Applications (18)

Applications Claiming Priority (2)

Publications (2)

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• 1998
  • 1998-07-07 DE DE19830201A patent/DE19830201A1/de not_active Withdrawn
• 1999
  • 1999-07-02 HU HU0103922A patent/HUP0103922A3/hu unknown
  • 1999-07-02 WO PCT/EP1999/004595 patent/WO2000002542A2/de not_active Ceased
  • 1999-07-02 PL PL99345842A patent/PL195043B1/pl not_active IP Right Cessation
  • 1999-07-02 EA EA200100084A patent/EA003142B1/ru not_active IP Right Cessation
  • 1999-07-02 CZ CZ200177A patent/CZ294087B6/cs not_active IP Right Cessation
  • 1999-07-02 DE DE59903556T patent/DE59903556D1/de not_active Expired - Fee Related
  • 1999-07-02 DK DK99934560T patent/DK1093369T3/da active
  • 1999-07-02 RS YUP-4/01A patent/RS49795B/sr unknown
  • 1999-07-02 YU YU401A patent/YU401A/sh unknown
  • 1999-07-02 IL IL14060399A patent/IL140603A0/xx not_active IP Right Cessation
  • 1999-07-02 ES ES99934560T patent/ES2183583T3/es not_active Expired - Lifetime
  • 1999-07-02 EP EP99934560A patent/EP1093369B1/de not_active Expired - Lifetime
  • 1999-07-02 ID IDW20010017A patent/ID27776A/id unknown
  • 1999-07-02 SK SK11-2001A patent/SK284923B6/sk not_active IP Right Cessation
  • 1999-07-02 CA CA002336833A patent/CA2336833C/en not_active Expired - Fee Related
  • 1999-07-02 TR TR2001/00146T patent/TR200100146T2/xx unknown
  • 1999-07-02 NZ NZ509729A patent/NZ509729A/xx unknown
  • 1999-07-02 CN CNB998083038A patent/CN1230168C/zh not_active Expired - Fee Related
  • 1999-07-02 AT AT99934560T patent/ATE228365T1/de not_active IP Right Cessation
  • 1999-07-02 KR KR1020017000088A patent/KR100557692B1/ko not_active Expired - Fee Related
  • 1999-07-02 PT PT99934560T patent/PT1093369E/pt unknown
  • 1999-07-02 AU AU50303/99A patent/AU762128B2/en not_active Ceased
  • 1999-07-02 BR BR9911768-1A patent/BR9911768A/pt not_active Application Discontinuation
  • 1999-07-02 JP JP2000558802A patent/JP2002520273A/ja active Pending
  • 1999-07-02 EE EEP200100014A patent/EE04296B1/xx not_active IP Right Cessation
  • 1999-07-06 US US09/348,591 patent/US6255329B1/en not_active Expired - Fee Related
  • 1999-07-06 TW TW088111454A patent/TW592698B/zh not_active IP Right Cessation
  • 1999-07-07 AR ARP990103294A patent/AR019896A1/es unknown
  • 1999-07-07 MY MYPI99002869A patent/MY117969A/en unknown
• 2001
  • 2001-01-03 BG BG105112A patent/BG64972B1/bg unknown
  • 2001-01-04 ZA ZA200100090A patent/ZA200100090B/en unknown
  • 2001-01-05 NO NO20010064A patent/NO20010064L/no not_active Application Discontinuation

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