CN117942336A - Use of Go6976 for preparing antidepressant drugs - Google Patents

Abstract

The invention belongs to the technical field of antidepressants, and relates to application of Go6976 in preparation of antidepressants. Go6976 has antidepressant property, and has definite, obvious and long-lasting treatment effect when used as antidepressant drug, and potential application value for treating depression.

Description

Use of Go6976 for preparing antidepressant drugs

Technical Field

The invention belongs to the technical field of antidepressants, and relates to application of Go6976 in preparation of antidepressants.

Background

Depression (Major depressice disorder, MDD) is a serious affective disorder, placing a serious burden on society, and today morbidity, disability rate, mortality are increasing. Currently, about 3.22 million global depression patients account for 4.4% of the world population, and have become the first non-fatal disabling disease worldwide. However, the pathogenesis of depression is not completely understood at present, and great challenges are brought to clinical treatment and development of new drugs.

Antidepressants (ANTIDEPRESSIVE DRUGS) are a group of psychotropic drugs that are mainly used to treat psychotic disorders with marked symptoms of mood depression. Antidepressants were introduced in the 50 s of the 20 th century, and there was no suitable pharmaceutical treatment for depressive disorders. After the 50 s of the 20 th century, antidepressants became the treatment option of choice for depressed patients. At present, the action mechanism of almost all antidepressants mainly relates to the transmission of monoamine neurotransmitters, has relatively more side effects and definite curative effects, but is not satisfactory, for example, part of patients are ineffective on almost all antidepressants, the action time of almost all antidepressants is longer, the antidepressants can take at least 2 weeks to take effect, and adverse reactions are relatively more. Although ketamine was approved by the FDA in 2019 for the treatment of depression, because ketamine has psychotropic and addictive properties, its clinical application is significantly limited and patients can only use it under the supervision of doctors in hospitals and cannot be taken home. Therefore, it is highly necessary to develop new rapid antidepressant molecules that do not have psychotropic and addictive properties.

Disclosure of Invention

The invention aims to provide an application of Go6976 in preparing antidepressant drugs. The antidepressant prepared from Go6976 has definite and remarkable antidepressant effect and small side effect.

To this end, the present invention provides the use of Go6976 for the preparation of an antidepressant.

Preferably, the effective dose of the antidepressant is Go6976 at a daily dose of 0.3256mg per kg of body weight.

In the present invention, the dosage form of the antidepressant includes an oral preparation or an injection preparation.

In the present invention, the oral preparation is selected from the group consisting of tablets, granules, capsules and pills.

In some embodiments of the invention, the amount of Go6976 per unit of preparation of the oral formulation is 75.973mg.

In the invention, the injection preparation is powder or injection.

In some embodiments of the invention, go6976 is present in an amount of 15.19-30.39mg per unit of formulation of the injectable formulation.

In some embodiments of the invention, the antidepressant drug produces an antidepressant-like effect within 24 hours of a single administration after successful CSDS molding.

In some embodiments of the invention, the antidepressant effect lasts for an effective period of >7 days after a single administration of the antidepressant drug.

According to the invention, the antidepressant further comprises a pharmaceutically acceptable auxiliary ingredient.

In the invention, the Go6976 serving as an antidepressant has antidepressant property, quick response, definite and obvious treatment effect, small side effect and great potential value for treating depression.

Drawings

The invention will be described in further detail with reference to the accompanying drawings.

FIG. 1 shows that Go6976 failed to significantly rescue depressive-like behavior induced by chronic social frustrating stress 1 hour after dosing; a: a behavioral testing timeline diagram; b: the tail-suspension test results show the immobility time of the mice during the test. C-D: open field behavioral outcome; c: the residence time of the mice in the central zone; d: total movement distance of mice during the test phase.

Meanwhile, fig. 1 also shows that 24 hours after single administration of Go6976, the detection behavior significantly rescues the depression-like behavior induced by chronic social frustration stress, and the anxiety-like behavior caused by chronic social frustration stress cannot be rescued; E-G is a social interaction test result, E: social interaction ratio; f: when no target strange CD-1 mouse exists; g: when a target strange CD-1 mouse exists, the residence time of the C57 mouse in a social interaction area is prolonged; h: a black-and-white box test result; showing the residence time of the mice in the white box; I-J is the open field behavioral outcome; i: the residence time of the mice in the central zone; j: total movement distance of mice during the test phase. K is a tail suspension test result, and shows the immobility time of the mice in the test process; l is the forced swimming result, showing the immobility time of the mice during the test. CSDS (chronic social related DEFEAT STRESS), CON (control group), SI (social interaction test ), OFT (open FIELD TEST, open field test), L/D box (light/dark box test), FST (forced swim test), TST (tail suspension test ). N=7-10 pieces/group. * p <0.05, < p <0.01, < p <0.001, < p <0.0001.

Figure 2 shows the maintenance time of antidepressant effect following administration of Go 6976; wherein, A is the 7 th day forced swimming result, showing the immobility time of the mice in the test process; b is a 7 th-day tail suspension test result, and shows the immobility time of the mice in the test process; c is the forced swimming result on the 10 th day, showing the immobility time of the mice in the test process; d is a10 th day tail suspension test result, and shows the immobility time of the mice in the test process; CSDS (chronic social DEFEAT STRESS), CON (control group), FST (forced swim test), TST (tail suspension test ). N=7-10 pieces/group. * p <0.05, < p <0.01, < p <0.001.

Detailed Description

In order that the invention may be readily understood, the invention will be described in detail below with reference to the accompanying drawings. Before the present invention is described in detail, it is to be understood that this invention is not limited to particular embodiments described. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

Unless defined otherwise, all terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described.

I terminology

The term "water" as used herein refers to pharmaceutical water, including purified water, water for injection or sterile water for injection, unless otherwise specified or limited.

The term "depression" in the present invention is also known as depressive disorder, and is characterized by a significant and persistent depression in mood as the main clinical feature, and is the main type of mood disorder. Clinically, the mood is dissatisfied with the mood, the mood can be subsided from smoldering to sad, sped down, even pessimistic pessimistic, and suicide attempts or behaviors can be achieved; even wood stiffness occurs; some cases have significant anxiety and motor agitation; in severe cases, psychotic symptoms such as hallucinations and delusions may occur. Each episode lasts at least 2 weeks, longer or even years, most cases have a tendency to recur, most of each episode can be alleviated, some can have residual symptoms or be converted to chronic.

The depression in the present invention includes depression in a general sense and depression or depression state induced by psychological and social factors, or depression state induced by any other somatic factors, and can be depression or depression state induced by brain trauma, cardiovascular and cerebrovascular diseases, cancers and other diseases, and treatment drugs such as interferon, anticancer drugs and the like used in cancer treatment, life or social rhythm disorder, chronic sleep disorder, long-term active stay up, chronic body diseases such as chronic pain, diabetes, liver diseases, kidney diseases, nervous system degenerative diseases and the like, and the like.

The depression-like and anxiety-like behavior in the present invention means that since animals cannot express their affective changes in language, it is only possible to infer whether they are depressed or anxiety by means of the animal's behavior. Thus, depression or anxiety in animals can only be described by words like depression or anxiety. Is equivalent to the manifestations of depression and anxiety in humans.

II. Embodiment

The existing antidepressant has relatively more side effects and definite curative effect, but is not satisfactory, and part of patients are ineffective to almost all antidepressants, and the onset time of almost all antidepressants is longer, so that the antidepressant takes at least 2 weeks to take effect. In view of this, the present inventors have long engaged in studying the pathogenesis of depression and the rapid antidepressant mechanism.

In a large number of long-term researches on the pathogenesis of depression and the rapid antidepressant mechanism, the inventor unexpectedly discovers that Go6976 has antidepressant effect and has longer curative effect maintenance time. The present invention has been made based on the above findings.

Accordingly, the present invention relates to the use of Go6976 for the preparation of an antidepressant.

The molecular structural formula of Go6976[12- (2-cyanoethyl) -6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo [2,3-a ] pyrrolo [3,4-C ] carbazole, 12H-Indolo [2,3-a ] pyrrolo [3,4-C ] carbazole-12-propanenitrile,5,6,7,13-tetrahydro-13-methyl-5-oxo- ] is shown as formula (I), and the chemical formula is C ₂₄H₁₈N₄ O.

Go6976 is a small molecule inhibitor of Protein Kinase C (PKC). Up to now, the medical community has not advanced the use of Go6976 for the treatment of depression. However, the inventor finds that Go6976 has better antidepressant activity by accident on the basis of long-term rapid antidepressant mechanism research, and uses certain dosage and concentration of Go6976 for treating depression, so that the effect is quick, the treatment effect is definite and obvious, the curative effect maintenance time is longer, and the side effect is smaller.

The GO6976 can be obtained through artificial synthesis or can be obtained directly and commercially (for example, abMole China), and the purity of the GO6976 is more than or equal to 98%.

According to the invention, the effective dose of the antidepressant is Go6976 at a dose of 0.3256mg per kg of body weight per day.

The drug effect dose of the antidepressant drug for human is estimated based on the drug effect dose of the mouse by the equivalent dose ratio of the human and the animal according to the body surface area conversion in the reference of the pharmaceutical experiment methodology of human (Xu Shuyun professor, P1861 table 11-8), and the weight of the mouse is calculated by 23.5 g.

In the present invention, the dosage form of the antidepressant includes an oral preparation or an injection preparation.

In the present invention, the content of Go6976 per unit of preparation of the Go6976 oral preparation is estimated based on 10% of the bioavailability of the Go6976 oral preparation.

In the present invention, the content of Go6976 per unit of preparation of the Go6976 injection formulation is estimated based on 75% of the bioavailability of the Go6976 injection formulation.

According to some embodiments of the invention, the oral formulation is selected from the group consisting of tablets, granules, capsules and pills, and the Go6976 content per formulation unit is 75.973mg, 3 times a day.

Based on the above, it is easy to understand that the usage and the dosage of the antidepressant oral preparation in the invention are as follows: 3 times daily, 1 formulation unit each time. For example, the antidepressant oral dosage form may be administered at 75.973mg each time, 3 times daily.

According to other embodiments of the present invention, the injectable formulation is a powder or an injectable solution, and the content of GO6976 per formulation unit of the injectable formulation is 15.19-30.39mg, 1-2 times daily.

Based on the above, it is easy to understand that the usage and the dosage of the antidepressant drug preparation injection preparation in the invention are as follows: 1-2 times daily, 1 formulation unit each time. For example, the antidepressant may be administered intravenously in an amount of 15.19-30.39mg each time, 1-2 times daily.

In some embodiments of the invention, the antidepressant drug produces an antidepressant-like effect within 24 hours of a single administration after successful modeling of CSDS, and the antidepressant effect persists for an effective period of >7 days after a single administration.

According to the invention, the antidepressant further comprises a pharmaceutically acceptable auxiliary ingredient.

In the present invention, pharmaceutically acceptable auxiliary ingredients are not particularly limited, and those conventionally used in the art may be employed.

For example, for tablets, the pharmaceutically acceptable auxiliary ingredients include fillers (diluents, absorbents), wetting agents, binders, disintegrants, lubricants and other surfactants.

The filler comprises one or more of starch, sugar powder, dextrin, lactose, pregelatinized starch, microcrystalline cellulose, inorganic salts and mannitol.

The wetting agent and binder comprise one or more of water, ethanol, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, and other binders (gelatin solution, sucrose solution, and aqueous or alcoholic solution of polyvinylpyrrolidone).

The disintegrating agent comprises one or more of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crosslinked polyvinylpyrrolidone and crosslinked sodium carboxymethyl cellulose.

The lubricant comprises one or more of magnesium stearate, talcum powder, hydrogenated vegetable oil, micro silica gel, polyethylene glycol and magnesium laurel sulfate.

Such other surfactants include sodium dodecyl sulfate and the like for improving the dissolution rate.

As another example, since GO6976 is a fat-soluble compound, for injection, pharmaceutically acceptable auxiliary ingredients mainly include vehicle ingredients including, but not limited to DMSO, corn oil, and the like.

It will be appreciated by those skilled in the art that for powder-type injections, the antidepressant powder formulations of the present invention may be dissolved or dispersed in DMSO and/or corn oil for use to make an injection.

It is readily understood that injection-type injectables are made from the antidepressant of the present invention dispersed in DMSO and/or corn oil. Meanwhile, the bioavailability of the GO6976 is improved due to higher liposolubility than water solubility, such as liposome, self-microemulsion preparation, solid lipid nano-particles and the like.

In some specific preferred examples of the invention, go6976 is fat-soluble in a ratio of DMSO to corn oil=1:9 to obtain a stock solution with a higher molar concentration. The stock solution was diluted to 2.5mg/ml in PBS and the mice were injected.

The related test method in the invention is as follows:

1. A model of Chronic social stress-controlling depression (Chronic Association DEFEAT STRESS (CSDS) (10 consecutive days, once daily stress) was established using male, adult wild-type C57BL/6J mice.

Chronic social frustrating stress is consistent with previous literature reports. One single C57BL/6J invader mouse was contacted with different CD-1 challenged mice for 10 minutes daily for 10 days. After CSDS, the C57BL/6J mice were housed in the same cage as the CD-1 challenged mice, separated by a perforated plexiglass spacer, allowing the C57BL/6J mice to receive sensory contact stress from the CD-1 mice for the remaining 24 hours. Control C57BL/6J mice were placed in cages separated by a spacer, one on each side. Mice in the control group were replaced once daily. All stressed and control animals were subjected to behavioral testing in sequence starting on day 10.

2. Go6976 was given by intraperitoneal injection at 2.5mg/kg the day after the end of CSDS. Tail suspension and open field behaviours of mice were measured at 1h, 3h, respectively. The purpose of the 1h test tail suspension was to detect whether Go6976 had a rapid antidepressant effect 1 hour after administration, and the 3h test field was to detect whether Go6976 had an acute sedative effect or had an effect on motor ability in mice.

3. The following day after single administration, social interaction test, open field experiment, black and white box experiment, tail suspension test and forced swimming test are continued. The tail suspension test and the forced swimming test were performed again on the 7 th and 10 th days after the single administration in order to detect the duration of the antidepressant effect of Go 6976.

3.1 Social interaction test (social interaction, SI)

Social avoidance behavior simulates behavior such as reluctant to go out, to see a person, to speak, to avoid normal social activities, etc. of a depression patient in real life, and is measured by a two-stage SI test. In the first stage, the animals were placed in an open field (44X 44cm ³) with an iron cage (cylindrical shape with a bottom diameter of 9cm and a height of 8 cm). The time taken in the area around the railing cage (interaction area, area 8cm around) and in the area of the wall opposite the cage (opposite area, area 9cm opposite the cage close to the wall) was measured. The time spent in the interaction area in the first phase is called "no target". The animals were then returned to home cage for 1 minute. In the second phase, an offensive strange CD-1 mouse is placed in the iron cage and the same index is measured, and the time spent in the interaction area is called "target". From the statistics of these two phases, the SI index (time spent in the Target's interaction region/time spent in the No Target's interaction region) is calculated. When the index is <1, the animals are considered to be stress-susceptible (SUS), the model modeling of depression is successful, and when the index is >1, the animals are considered to be stress-Resistant (RES), and the animals do not exhibit depression-like behavior.

3.2 Forced swim test (forced SWIMMING TEST, FST)

FST was performed in a transparent glass cylinder (45 cm high, 19cm diameter) with a water depth of 23cm and a water temperature of 22-25 ℃. The test was continued for 6 minutes and the rest time was counted for the last 5 minutes.

3.3 Tail suspension test (tail suspended test, TST)

One end of the adhesive tape is fixed at the 1/3 position of the tail end of the tail of the mouse, the other end of the adhesive tape is fixed on an acrylic rod at the top of a tail suspension test box, the total suspension time of the mouse is 6 minutes, and the rest time of the mouse in the last 5 minutes is counted.

3.4 Open field test (open FIELD TEST, OFT)

The mice were placed in an open field (44X 44cm ³), and allowed free exploration for 5 minutes. The residence time of the mice in the central zone (18X 18cm ²) and the total movement distance of the horizontal movement of the mice were counted.

3.5 Black and white Box test (light/dark box, LD box)

The black-and-white box test is carried out in a black-and-white box with the dimensions of 45cm multiplied by 27cm (length, width and height), half of the black-and-white box is a darkroom, half of the black-and-white box is a bright room, and a small hole is formed in the middle of the black-and-white box to be connected for animals to pass through. Mice were placed in the bright room, allowing free exploration for 5 minutes. During this time, the time and shuttle times of mice in the white and black boxes were recorded.

III. Examples

The present invention will be specifically described below by way of specific examples. The experimental methods described below, unless otherwise specified, are all laboratory routine methods. The experimental materials described below, unless otherwise specified, are commercially available.

The quantitative experiments in the following examples were all set up in triplicate, all results being expressed as Mean ± standard error (Mean ± s.e.m). Data were analyzed using Two-Way ANOVA (Two-Way ANOVA), post hoc analysis was performed using Bonferroni test with p <0.05 as the difference significance standard.

The experimental animals were male C57BL/6J mice (6-8 weeks old, 22-25 g) purchased from Experimental animal department of medicine, beijing university. Male CD-1 mice (7-9 months old) were purchased from Peking Vitre Liwa laboratory animal technologies Co. All mice had a1 week adaptation time before the CSDS experiment began. C57BL/6J mice were placed in animal houses at 4-5 per cage, CD-1 mice were placed in animal houses at 1 per cage, the temperature (22.+ -. 2 ℃) humidity (50.+ -. 10%) and illumination time (12 h light/dark alternation, 20:00pm on lamp, 8:00am off lamp) were kept fixed in the house, and food and water were freely available, and the behavioural tests were all performed in the dark period.

All operations accepted by the experimental animals are in accordance with the ethics of the experimental animals, and follow the regulations issued by the animal use and protection committee of the university of Beijing, medical department of China.

Go6976 was fat-dissolved in DMSO at a ratio of corn oil=1:9 to give a stock solution with a higher molar concentration. The stock solution was diluted to 2.5mg/ml in PBS and the mice were injected.

Example 1: go6976 initiates a behavioral test 1 hour after dosing and 24 hours after dosing markedly rescues depression-like behavior induced by chronic social frustration stress, failing to rescue anxiety-like behavior induced by chronic social frustration stress.

First, we wanted to explore whether Go6976 had a rapid antidepressant effect, so we performed tail-suspension and open field tests at 1 hour and 3 hours after Go6976 administration, respectively. The open field test was performed to investigate whether Go6976 would cause acute sedation or inhibition of motor ability in mice. Results from the tail-suspension test 1 hour after dosing showed no significant interaction effect between Go6976 and CSDS (F (_1,35) =3.737, p= 0.0613), further post hoc analysis (post hoc analysis with Bonferroni test), significant rise in immobility time in the mouse tail-suspension test after CSDS, no significant reversal of depression-like behavior in mice 1 hour after dosing (fig. 1B,CON+PBS VS CSDS+PBS,p = 0.0249;CSDS+PBS VS CSDS+Go6976,p = 0.9323). The open field test results at the 3 hour time point of dosing showed that the residence time of the mice in the central zone was significantly reduced after CSDS (fig. 1C,CON+PBS VS CSDS+PBS,p =0.0017), showing anxiety-like behavior, while Go6976 had no significant effect on this behavior (csds+pbs VS csds+go6976, p= 0.9573). The movement distance of the csds+go6976 mice in the open field is significantly lower than that of the csds+pbs group mice (fig. 1D,CSDS+PBS VS CSDS+Go6976,p = 0.0213), indicating that Go6976 has no effect on the movement ability of normal non-model mice, and may have potential inhibitory or sedative effects on the movement ability of post-model depression-like mice, requiring further movement ability behavioral tests to illustrate.

Go6976 was able to rescue depression-like behavior induced by chronic social frustration stress 24 hours after dosing, SI behavioural results showed that there was a significant interaction effect between Go6976 and CSDS (F (_1,35) =7.870, p=0.0082), further post hoc analysis (post hoc analysis using Bonferroni test), the social interaction rate of mice was significantly reduced after CSDS, go6976 reversed the social behavior impairment of mice (fig. 1E-G, con+pbs VS csds+pbs, p= 0.0011;CSDS+PBS VS CSDS+Go6976,p =0.0255). In the black and white box experiments, the residence time of mice in the white box after CSDS was significantly reduced, showing anxiety-like behavior (fig. 1H,CON+PBS VS CSDS+PBS,p =0.0087), while Go6976 had no significant effect on this behavior (csds+pbs VS csds+go6976, p=0.9999). In open field experiments, mice showed significantly reduced residence time in the central zone after CSDS (fig. 1I,CON+PBS VS CSDS+PBS,p =0.0002), showing anxiety-like behavior, while Go6976 had no significant effect on this behavior (csds+pbs VS csds+go6976, p= 0.1808). There was no significant difference in the distance traveled by each group of mice in the open field (fig. 1J). The tail suspension test results show that there is a significant interaction effect between Go6976 and CSDS (F (_1,33) =35.14, p < 0.0001), the tail suspension time of mice after CSDS is significantly increased, go6976 reverses the tail suspension time of mice, making it significantly reduced (fig. 1K,CON+PBS VS CSDS+PBS,p<0.0001;CSDS+PBS VS CSDS+Go6976,p =0.0003). The forced swimming test results show that there is a significant interaction effect between Go6976 and CSDS (F (_1,32) =4.638, p= 0.0389), the immobility time of the mice for forced swimming after CSDS increases significantly, and Go6976 reverses the immobility time of the mice for forced swimming, causing it to decrease significantly (fig. 1L,CON+PBS VS CSDS+PBS,p = 0.0023;CSDS+PBS VS CSDS+Go6976,p = 0.0395). Overall, significant depression-like and anxiety-like behavior was produced after CSDS in mice, go6976 had a rescue effect on CSDS-induced depression-like behavior, and focus-like behavior did not show a rescue effect.

Example 2: duration of antidepressant action of Go6976

To test the duration of antidepressant effect of Go6976, we performed the tail-hanging and forced swimming test again on day 7, day 10 after one intraperitoneal injection of Go 6976. The tail-biting test results on day 7 showed that there was no significant interaction effect between Go6976 and CSDS (fig. 2a, f (_1,36) =1.770, p=0.1918). The forced swimming test results show that there is a significant interaction effect between Go6976 and CSDS (F (_1,36) =14.35, p=0.0006), after CSDS the immobility time of the forced swimming of the mice is significantly increased, go6976 reverses the immobility time of the forced swimming of the mice, making it significantly reduced (fig. 2B,CON+PBS VS CSDS+PBS,p = 0.0135;CSDS+PBS VS CSDS+Go6976,p =0.0051). The tail-biting test results on day 10 showed that there was no significant interaction effect between Go6976 and CSDS (fig. 2c, f (_1,32) =1.351, p= 0.2537). The forced swimming test results showed that there was no significant interaction effect between Go6976 and CSDS (fig. 2d, f (_1,33) =1.364, p= 0.2512), the immobility time of the mice forced swimming after CSDS was significantly increased, but Go6976 failed to reverse the forced swimming immobility time of the mice (fig. 2D,CON+PBS VS CSDS+PBS,p = 0.0398;CSDS+PBS VS CSDS+Go6976,p =0.9967). Overall, go6976 still exerts an antidepressant effect on day 7 after intraperitoneal injection of Go6976, but this effect is lost on day 10.

It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and are used for explaining the present invention, not to be construed as limiting the present invention. The invention has been described with reference to exemplary embodiments, but it is understood that the words which have been used are words of description and illustration, rather than words of limitation. Modifications may be made to the invention as defined in the appended claims, and the invention may be modified without departing from the scope and spirit of the invention. Although the invention is described herein with reference to particular means, materials and embodiments, the invention is not intended to be limited to the particulars disclosed herein, as the invention extends to all other means and applications which perform the same function.

Claims (10)

1. Use of Go6976 for the preparation of an antidepressant.

2. The use according to claim 1, wherein the antidepressant is administered in a pharmaceutically effective amount of Go6976 at a daily dose of 0.3256mg per kg of body weight.

3. The use according to claim 2, wherein the dosage form of the antidepressant comprises an oral or injectable formulation.

4. The use according to claim 3, wherein the oral formulation is selected from the group consisting of tablets, granules, capsules and pills.

5. The use according to claim 4, wherein the content of Go6976 per unit of preparation of the oral formulation is 75.973mg.

6. The use according to claim 3, wherein the injectable formulation is a powder or an injectable solution.

7. The use according to claim 6, wherein Go6976 is present in an amount of 15.19-30.39mg per unit of preparation of the injectable formulation.

8. The use according to any one of claims 1 to 7, wherein the antidepressant drug produces an antidepressant-like effect within 24 hours of a single administration after successful CSDS molding.

9. The use according to any one of claims 1-8, wherein the antidepressant is effective for a period of >7 days after a single administration of the antidepressant.

10. The use according to any one of claims 1 to 9, wherein the antidepressant further comprises a pharmaceutically acceptable auxiliary ingredient.