Method of treating or preventing mood disorders, mental disorders, and/or chronic fatigue syndrome

Abstract

A method of treating or preventing mood disorders, mental disorders, and/or chronic fatigue syndrome is provided. The method comprises administering to a subject in need thereof a pharmaceutical composition containing one or more kinds of compounds of the following structure: ##STR00001## wherein R is an alkyloxy group containing 1 to 3 carbon atoms or a halogen group.

Claims

1. A method of treating depression, and/or chronic fatigue syndrome, comprising administering to a subject in need thereof a pharmaceutical composition containing one or more kinds of compounds of the following structure: ##STR00006## wherein R is an alkyloxy group containing 1 to 3 carbon atoms or a halogen group.

2. The method according to claim 1, wherein R is a methoxy group or a chloro group.

3. The method according to claim 1, wherein the compound is chlorphenesin carbamate and/or methocarbamol.

4. The method according to claim 1, wherein the pharmaceutical composition includes both chlorphenesin carbamate and methocarbamol.

Description

EXAMPLE

(1) Animal Experiments

(2) The antidepressant action of a test substance may be evaluated using a “forced swimming method” in a mouse model.

(3) The forced swimming test in mouse models is an animal experimental method for confirming the antidepressant activity proposed by Porsalt (Arch. Int, pharmacydn. 229.327-336 (1977)).

(4) A mouse placed into a pool indicates either an active state or a non-moving state. Decreases in the non-moving state of the mouse is used as an index to confirm the antidepressant action of a pharmaceutical composition.

(5) 1. Pool for Forced Swimming

(6) The pool used for forced swimming was a glass cylindrical container 30 cm in height and 16 cm in inner diameter filled at a water depth of 20 cm at 25° c.

(7) 2. Test Animal

(8) Animal species: mouse

(9) System: S1c: ICR

(10) Sex: male

(11) Supply source: Japan LSC Co. Ltd.

(12) Microbiological grade: SPF

(13) Age on arrival day: 8 weeks old

(14) Age on test day: 9 weeks old

(15) Individual identification: A label describing test number, cage number, and individual identification number was installed in the cage. An individual identification number was written on the tail of the animal.

(16) 3. Substances Used for Testing and Preparing the Pharmaceutical Composition Used in the Test

(17) Methocarbamol was used in this test of the present invention.

(18) Etizolam was used as a comparative example with the present invention, which is commonly used as an antianxiety agent in the treatment of depression.

(19) A 260 mg methocarbamol formulation (manufactured by Ying-Yuag chemical pharmaceutical Co. Ltd., product name bolaxin, methocarbamol content: 76% mass) was added to the distilled water until reaching a volume of 10 mL, and 200 mg of the distilled water/10 ml of a methocarbamol aqueous solution (2% mass in terms of methocarbamol) was prepared (reagent name M-1).

(20) A 3.3 mg etizolam formulation (trade name etilaam-1, etizolam content: 0.01 mass %, produced by INTAS PHARMACEUTICAL Co. Ltd.) was also added to the distilled water until reaching a volume of 10 mL, and 0.033 mg of the distilled water/10 ml of etizolam aqueous solution (0.00033% mass in terms of etizolam) was prepared (reagent name E-1). Table 1 below shows the dose for each mouse.

(21) TABLE-US-00001 TABLE 1 Ingredient name Dosage amount Example (Reagent M-1 Methocarbamol 200 mg/kg administration group) Comparative example Etizolam 0.033 mg/kg (Reagent E-1 administration group)

(22) 4. Forced Swimming Test

(1) Embodiment 1

(23) One hour before the test, 10 mL/kg of the above prepared methocarbamol aqueous solution was administered to the mouse only once (200 mg/kg in methocarbamol conversion).

(24) The administration route was a forced oral administration using an installed mice oral administration sonde made by FUCHIGAMI with a syringe for injection made by TERUMO.

(25) The method was carried out under non-anesthesia.

(26) After one hour of forced administration, the mouse was placed in the forced swimming pool described above and left for 10 minutes.

(27) The first three minutes after entering were considered a conditioning period, and the mouse's non-moving time in the remaining 7 minutes was measured.

(28) “Non-motion” was defined by the mouse not moving the anterior limb and the posterior limb, and by a state in which the upper side of the neck is lifted from the water surface and floats.

(29) The “non-moving time” was the sum of “non-motion” time.

(30) The test was repeated 10 times for each mouse, and an average value was calculated.

(2) Comparative Example

(31) An etizolam aqueous solution was used in place of a methocarbamol aqueous solution. The same test as described above (1) was performed, but with the administration amount converted to etizolam usage at 0.0333 mg/kg.

(3) Medium Control

(32) Distilled water not containing a pharmaceutical was used in place of the methocarbamol aqueous solution in the same manner as described above (1).

(33) 5. Results

(34) The average non-moving time values of the medium control group (n=10), the examples, and comparative examples (n=10) were compared with each other.

(35) Table 2 below shows the average values.

(36) TABLE-US-00002 TABLE 2 Immobile time average Administration group value (sec) standard deviation Medium handling group 230.8 17 Example (Reagent M-1 157.7 20.1 administration group) Comparative example 107.3 18.5 (Reagent E-1 administration group)

(37) The “non-moving time” was 230.8 seconds in the medium control group, 107.3 seconds in the etizolam control group, and 157.7 seconds in the methocarbamol dose group. Thus, it is apparent that the methocarbamol administration group had essentially the same effect as the etizolam administration group.

(38) Test for administration to depression patients (embodiment 1)

(39) 1. Treatment of Depression Patients

(40) Preparation of pharmaceutical compositions comprising (1) methocarbamol

(41) A 500 mg bolaxin tablet (manufactured by Ying-Yuan chemical pharmaceutical co. ltd.) and 500 mg-containing (methocarbamol content 76% mass) were prepared.

(42) 2. Patient

(43) A subject suffering from depression for two or more years was selected.

(44) 3. Treatment Method

(45) A pharmaceutical composition was administered to the patient three times a day, and the administration was continued for one week.

(46) The dose on the initial day was 3.0 to 4.5 g/day (converted to methocarbamol).

(47) After observing the patient's state, it was increased to 6.0 g/day (converted to methocarbamol).

(48) (all doses were recorded).

(49) The regular drug in addition to the tested pharmaceutical composition was continuously taken, but drinking was prohibited during the test.

(50) 4. Judgment of Results

(51) After one week, a potential depression improvement effect before and after administration was evaluated.

(52) The evaluation investigated a significant difference in two-term judgment of two related groups.

(53) The evaluation was judged based on a declaration of whether the subjects felt an improvement in thinking, desires, and fatigue.

(54) 5. Results

(55) Table 3 below shows the test results after one week.

(56) TABLE-US-00003 TABLE 3 N number 5 persons Effective 5 persons No effect 0 persons

(57) As described above, it was confirmed that a pharmaceutical composition containing methocarbamol had a beneficial depression treatment effect.

INDUSTRIAL APPLICABILITY

(58) The present invention provides an alternative pharmaceutical composition for patients who have not been treated with SSRIs or similar drugs, patients who are resistant to the beneficial effects of SSRIs. This invention aims to decrease side effects relative to treatment with SSRIs and provide a method for more effective treatment and/or prevention of mood disorders, mental disorders, and/or chronic fatigue syndrome.