JP2001520194A - Use of moxonidine for the treatment of depression - Google Patents

Abstract

  (57) [Summary] Use of moxonidine or a pharmaceutically acceptable acid addition salt thereof in the manufacture of a medicament for treating a central nervous system disease.

Description

DETAILED DESCRIPTION OF THE INVENTION

Moxonidine is a compound well known for its antihypertensive properties, for example, as described in US Pat. No. 4,323,570. The compound has the chemical formula 4-chloro-6-methoxy-2-methyl-5- (2-imidazolin-2-yl) aminopyrimidine.

It has now been found that moxonidine is indicated for use in treating depression.

[0003] Accordingly, the present invention includes the use of moxonidine, or a pharmaceutically acceptable acid addition salt thereof, in the treatment of depression. More specifically, the present invention includes the use of moxonidine, or a pharmaceutically acceptable acid addition salt thereof, in the manufacture of a medicament for treating depression.

In a test model, moxonidine was found to significantly modulate α2-adrenoceptor and adrenergic receptor agonist properties. This is, for example, as described in Cervo et al. (1992) Neuropharmacology, 31, 331-335.
Proven by the well-known forced swim test.

[0005] As mentioned above, moxonidine is the compound 4-chloro-6-methoxy-2-methyl-5- (2-imidazolin-2-yl) aminopyrimidine, which is a pharmaceutically acceptable acid addition salt. It can be used in form. Suitable acid addition salts include suitable acids, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid or phosphoric acid, glycolic acid, maleic acid, hydroxymaleic acid, fumaric acid, malic acid, tartaric acid, citric acid. Pharmaceutically acceptable non-toxic with acids, salicylic acid, O-acetoxybenzoic acid, or organic carboxylic acids such as organic sulfuric acid, 2-hydroxyethanesulfonic acid, toluene-p-sulfonic acid, or naphthalene-2-sulfonic acid It is an addition salt.

[0006] Treatment of depression is described, for example, in the Diagnostic and Statistical Manual of Mental Di
sorders, as defined in the American Psychiatric Association, Fourth Edition (DSM-IV), the following diseases, namely the occurrence of major depression, major depression,
Various associated mood disorders such as thymic dysfunction, the development of unspecified depression, bipolar and circulatory disorders, and depression with anxiety
Including treatment.

[0007] The identification of a patient in need of treatment for depression is a routine matter, and if a patient requires treatment, a skilled clinician can use clinical trials, physical examination and medical / family histories. It can be easily determined.

For the purposes of the present invention, moxonidine is administered orally or rectally, in the form of commonly used pharmaceutical compositions, topically, or parenterally, such as by injection or infusion.
Such compositions are manufactured in a manner well-known in the art of pharmacy. In preparing the compositions, the active ingredient will usually be mixed with or diluted with a carrier, and / or enclosed in a carrier, for example, in the form of a capsule, sachet, paper, or other container. When the carrier is supplied as a diluent, it may be a solid, semi-solid or liquid material that acts as a vehicle, excipient or medium for the active ingredient. Thus, the composition comprises tablets, medicinal drops, sachets, cachets, elixirs.
s), suspensions, aerosols (as solid or in liquid medium), for example ointments, soft and hard capsules, suppositories, injections, suspensions, sterile containerized powders and up to 10% by weight of active ingredient and This is a form as a local patch. Preferred formulations are for oral administration, especially in the form of tablets or capsules.

Some examples of suitable carriers include lactose, glucose, sucrose, sorbitol, mannitol, starch, ethyl cellulose, gum acacia, calcium phosphate, alginate, tragacanth, gelatin, syrup, methylcellulose, methyl- And propyl hydroxyhydroxybenzoate, magnesium talc stearate and mineral oil. Injectable compositions, as is well known in the art,
After administration to a patient, the active ingredients are formulated to provide rapid, sustained or delayed release.

When the compositions are formed in unit dosage form, each unit form may be 0.01 mg to 2.0 mg, for example 0.05 mg to 1.0 mg, as the amount associated with the active ingredient as the free base. Preferably, it contains 0 mg. The term "unit dosage form" is referred to as physically discrete units suitable as unit dosages for human subjects and animals, each unit being associated with a required pharmaceutical carrier to produce the desired therapeutic effect. Contains the calculated expected amount of active substance.

The active compound is effective over a wide dosage range, for example, daily dosages typically ranging from 0.01 to 2.0 mg, more usually from 0.1 to 1.0 mg. It is. Usually, once daily dosing, preferably once in the morning, is sufficient. It will be understood, however, that the dosage will be determined by the physician in view of the condition to be treated and the relevant circumstances including the chosen route of administration. Therefore, the above dosage ranges are not intended to limit the scope of the invention.

The following example illustrates the activity of moxonidine in a mouse model. Before you can use the example experiment, it was housed two weeks female mice in the facility. Immobile state (i
mmobility) in 11 beakers filled with 600 ml of water (10 cm deep)
At 23 ° C. The time spent immobile was measured with a stopwatch. Animals were removed from their cages and placed in individual cages (10 x 15 x 13 cm) for at least 60 minutes before the start of the experiment. Animals were dosed with moxonidine and returned to their cages for 30 minutes. When the pretreatment time had elapsed, the animals were placed in beakers and the time spent immobile was recorded. Animals were placed in beakers for 5 minutes. Immobility was not initially measured since all animals were swimming at this time almost independently of treatment. Minimum of 6 for each group
One animal was tested. Moxonidine reduced the time spent immobile in the forced water test. Moxonidine was active at all concentrations tested (2.5-10 mg / kg). The effect observed was 10 mg / k included as a positive control.
g of imipramine.

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Claims (3)

[Claims] 1. Use of moxonidine or a pharmaceutically acceptable acid addition salt thereof in the manufacture of a medicament for treating a central nervous system disease. 2. Use according to claim 1, wherein the drug is in a unit dosage form containing 0.01 to 2.0 mg of moxonidine. 3. A method of treating an animal, including a human, suffering from or susceptible to depression, comprising administering an effective amount of moxonidine, or a pharmaceutically acceptable acid addition salt thereof.