Pharmaceutical composition

Abstract

Provided is a novel therapeutic or prophylactic agent for psoriasis. A psoriasis therapeutic or prophylactic agent which contains a serotonin 4 receptor agonist.

Description

Technical Field

[0001] The present invention relates to an agent for treating or preventing psoriasis. Background Art

[0002] Psoriasis is a chronic inflammatory skin disease with a global prevalence of 2%. Psoriasis is characterized by scaling, redness, hypertrophy, severe flaking, and inflammation of the skin in various parts, accompanied by itching, which may have a very serious psychosocial impact on the patient's quality of life and health.

[0003] The treatment of psoriasis mainly uses topical medications, oral medications, biological preparations, and light therapy.

[0004] In recent years, oral medications for treating psoriasis have been developed that contain PDE4 inhibitors (eg, Apremilast) as active ingredients.

[0005] Non-patent document 1 describes that the incidence of mild psoriasis requiring whole-body radiation therapy is reduced by half in patients taking SSRI (Selective Serotonin Reuptake Inhibitor).

[0006] However, it is still unknown whether serotonin 4 receptor agonists are effective in the treatment and prevention of psoriasis.

[0007] Prior art literature

[0008] Non-patent literature

[0009] Non-patent literature 1: Shirin ESKELAND et al., Acta Derm Venereol 2017; 97: 897-905 Summary of the invention

[0010] Problems to be solved by the invention

[0011] The object of the present invention is to provide a novel agent for treating or preventing psoriasis.

[0012] Methods used to solve problems

[0013] The present inventors conducted intensive research to solve the above problems and surprisingly found that mosapride, which has a gastrointestinal motility promoting effect and is widely used to improve gastrointestinal symptoms, is effective for psoriasis. The present inventors conducted further research and found that a compound group having a serotonin 4 receptor agonist effect is effective for the treatment and prevention of psoriasis, thereby completing the present invention.

[0014] That is, the present invention is as follows.

[0015] [1] A therapeutic or preventive agent for psoriasis, comprising a serotonin 4 receptor agonist.

[0016] [2] The preparation according to [1] above, wherein the serotonin 4 receptor agonist is one or more selected from the group consisting of mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

[0017] [3] The preparation according to [1] or [2] above, which is for oral administration.

[0018] [4] A method for treating or preventing psoriasis, comprising the step of administering an effective amount of a serotonin 4 receptor agonist to a subject.

[0019] [5] The method according to [4] above, wherein the serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

[0020] [6] The method according to [4] or [5] above, wherein the administration is oral administration.

[0021] [7] A serotonin 4 receptor agonist for use in the treatment or prevention of psoriasis.

[0022] [8] The serotonin 4 receptor agonist according to [7] above, wherein the serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

[0023] [9] The serotonin 4 receptor agonist according to [7] or [8] above, which is used for oral administration.

[0024]

[10] Use of a serotonin 4 receptor agonist for the manufacture of a therapeutic or preventive agent for psoriasis.

[0025]

[11] The use according to

[10] , wherein the serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

[0026]

[12] The use according to

[10] or

[11] above, wherein the psoriasis therapeutic or preventive agent is for oral administration.

[0027]

[13] A therapeutic or preventive agent for psoriasis, comprising a serotonin 4 receptor agonist.

[0028]

[14] The preparation according to

[13] above, wherein the serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinipride, clebopride, fenfluramine, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, and pharmaceutically acceptable salts thereof (preferably one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinipride, clebopride, and pharmaceutically acceptable salts thereof).

[0029]

[15] The preparation according to

[13] or

[14] above, which is administered orally.

[0030] Effects of the Invention

[0031] According to the present invention, a novel therapeutic or preventive agent for psoriasis can be provided.

[0032] The therapeutic or preventive agent for psoriasis of the present invention can be expected to have an excellent therapeutic or preventive effect on psoriasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The results of Test Example 1 are shown. In the figure, mg / kg means mg / kg body weight.

[0034] Figure 2 The results of Test Example 2 are shown. In the figure, mg / kg means mg / kg body weight.

[0035] Figure 3 The results of Test Example 3 are shown. In the figure, mg / kg means mg / kg body weight.

[0036] Figure 4 The results of Test Example 4 are shown. In the figure, mg / kg means mg / kg body weight.

[0037] Figure 5 The results of Test Example 5 are shown. In the figure, mg / kg means mg / kg body weight.

[0038] Figure 6 The results of Test Example 6 are shown. In the figure, mg / kg means mg / kg body weight.

[0039] Figure 7 The results of Test Example 7 are shown. In the figure, mg / kg means mg / kg body weight. DETAILED DESCRIPTION

[0040] The psoriasis therapeutic or preventive agent of the present invention (may be abbreviated as the preparation of the present invention in this specification) contains a serotonin 4 receptor agonist as an active ingredient.

[0041] In the present invention, examples of the serotonin 4 receptor agonist include mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, fenfluramine, felcisetrag, naronapride, usmarapride, retardin, tadalafil, tadalafil, serotonin ... Relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof, preferably mosapride, prucalopride, vistrag, tegaserod, cisapride, cinipride, clebopride, fecisella, naronapride, usmapride, revexepride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof, more preferably mosapride, prucalopride, vistrag, and pharmaceutically acceptable salts thereof. In the present invention, the serotonin 4 receptor agonist can be used alone or in combination of two or more.

[0042] In the present invention, when there is a solvate (such as a hydrate), the serotonin 4 receptor agonist is a concept that also includes the solvate (such as a hydrate).

[0043] In the present invention, pharmaceutically acceptable salts of mosapride include, for example, mosapride citrate (especially mosapride citrate dihydrate), pharmaceutically acceptable salts of prucalopride include, for example, prucalopride succinate, pharmaceutically acceptable salts of tegaserod include, for example, tegaserod maleate, pharmaceutically acceptable salts of cinipride include, for example, cinipride tartrate, pharmaceutically acceptable salts of clobopride include, for example, clobopride malate, pharmaceutically acceptable salts of renopride include, for example, renopride hydrochloride, pharmaceutically acceptable salts of renzapride include, for example, renzapride hydrochloride (especially renzapride hydrochloride dihydrate), and pharmaceutically acceptable salts of nalapride include, for example, nalapride hydrochloride.

[0044] The psoriasis therapeutic or preventive agent of the present invention can be administered orally or parenterally, and is preferably administered orally.

[0045] When the psoriasis therapeutic or preventive agent of the present invention is provided as a drug for oral administration, examples of the dosage form include tablets, capsules, powders, granules, lozenges, syrups, liquid preparations, suspensions, and emulsions.

[0046] When the psoriasis therapeutic or preventive agent of the present invention is provided in the form of a drug for non-oral administration, examples of dosage forms include injections, drops, percutaneous absorption preparations, ointments, creams, gels, lotions, sprays, foams, patches, suppositories, granules, nasal preparations, pulmonary preparations, eye drops, and the like.

[0047] The psoriasis therapeutic or preventive agent of the present invention can be used in combination with other drugs for treating or preventing psoriasis (for example, vitamin D3 derivatives, vitamin D2 derivatives, vitamin E, retinoids, steroids, immunosuppressive drugs, immunomodulatory drugs, nonsteroidal anti-inflammatory drugs, cyclooxygenase inhibitors, PDE4 inhibitors, TNF-α inhibitors, antihistamines, inhibitors of molecules involved in signal transduction, interleukin inhibitors, interleukin receptor antagonists, interleukins, MAPK inhibitors, tyrosine kinase inhibitors, cytokine production inhibitors, JAK inhibitors, T cell inhibitors, B cell inhibitors, metabolic antagonists, gold preparations, co-stimulatory molecule-related proteins and dihydroorotate dehydrogenase (DHODH) inhibitors) (hereinafter referred to as concomitant drugs).

[0048] The serotonin 4 receptor agonist (active ingredient in the present invention) and the concomitant drug may be formulated simultaneously and administered as a single formulation, or the serotonin 4 receptor agonist and the concomitant drug may be formulated separately and administered to the same subject simultaneously or with a time difference via the same route or different routes.

[0049] The psoriasis treatment or prevention agent of the present invention may be a pharmaceutical composition comprising a serotonin 4 receptor agonist and at least one pharmaceutically acceptable carrier.

[0050] The psoriasis therapeutic or preventive agent of the present invention can be produced, for example, by mixing a serotonin 4 receptor agonist with at least one pharmaceutically acceptable carrier according to a method known in the field of pharmaceutical preparations.

[0051] As the pharmaceutically acceptable carrier, there can be listed excipients, disintegrants, binders, flow agents, lubricants, etc. in solid preparations; solvents, dissolution aids, suspending agents, isotonic agents, buffers, pH adjusters, analgesics, etc. in liquid preparations; and bases, emulsifiers, wetting agents, stabilizers, stabilizers, dispersants, plasticizers, pH adjusters, absorption promoters, gelling agents, thickeners, preservatives, fillers, solubilizers, dissolution aids, suspending agents, etc. in semisolid preparations. Furthermore, additives such as preservatives, antioxidants, colorants, sweeteners, etc. can be used as needed.

[0052] The content of the serotonin 4 receptor agonist in the therapeutic or preventive agent for psoriasis of the present invention varies depending on the dosage form, the type of serotonin 4 receptor agonist, the dosage, etc., and can be appropriately selected.

[0053] In the therapeutic or preventive agent for psoriasis of the present invention, the content of the serotonin 4 receptor agonist may be, for example, 0.1 to 100% by weight of the entire preparation.

[0054] The therapeutic or preventive agent for psoriasis of the present invention is effective for treating or preventing psoriasis in a subject to which it is administered.

[0055] In the present invention, "psoriasis" includes psoriasis vulgaris, psoriatic arthritis, guttate psoriasis, psoriatic erythroderma, and pustular psoriasis.

[0056] In the present invention, "treatment" refers to the act of administering the preparation of the present invention to an individual who has developed psoriasis, and also includes the act of administering the preparation of the present invention to improve psoriasis, prevent or delay aggravation, maintain symptom relief, prevent recurrence, and prevent recurrence. In the present invention, "prevention" refers to the act of administering the preparation of the present invention to an individual who has not developed psoriasis, and also includes the act of administering the preparation of the present invention to prevent or delay the onset of psoriasis.

[0057] The psoriasis therapeutic or preventive agent of the present invention can be safely administered to humans and mammals other than humans (eg, mice, rats, hamsters, rabbits, cats, dogs, cows, horses, pigs, sheep, and monkeys).

[0058] The dosage of the psoriasis treatment or prevention agent of the present invention varies depending on the subject of administration, symptoms, dosage form, route of administration, etc. For example, in the case of oral administration to an adult patient (weighing about 60 kg), the amount of the active ingredient, i.e., the serotonin 4 receptor agonist, per day is generally 0.01 mg to 500 mg, preferably 0.1 mg to 50 mg, and more preferably 1 mg to 30 mg, once a day or in divided doses.

[0059] Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited to these Examples and Test Examples.

[0060] Example

[0061] The compounds used in the following Test Examples 1 to 5 and their abbreviations are shown in Table 1. The compounds used in the following Test Examples 6 and 7 and their abbreviations are shown in Table 2. In addition, serotonin is abbreviated as 5-HT.

[0062] [Table 1]

[0063]

[0064]

[0065] [Table 2]

[0066]

[0067] [Test Example 1] Effect of 5-HT4 receptor agonist (comparison with 5-HT1 receptor agonist and 5-HT2 receptor agonist)

[0068] In order to confirm the effect of 5-HT receptor 4 agonist on dermatitis in psoriasis model mice, the following test was performed.

[0069] Psoriasis model mice were prepared by repeatedly applying 15 mg / ear of imiquimod cream (manufactured by Mochida Pharmaceutical Co., Ltd., product name: Beselna cream) to the right auricle of BALB / cCrSlc male mice (9 weeks old) once a day for 4 days (Day 0 to Day 3). One hour before the application of the above-mentioned imiquimod, 10 mL / kg body weight of vehicle (0.5% methylcellulose (hereinafter abbreviated as 0.5% MC)), 3 mg / kg body weight of MSP (5-HT4 receptor agonist), 3 mg / kg body weight of RZT (5-HT1 receptor agonist), 3 mg / kg body weight of TDS (5-HT1 receptor agonist), 3 mg / kg body weight of LCS (5-HT2 receptor agonist) and 10 mg / kg body weight of APR (positive control) were orally administered (Day 0 to Day 3) (n=6 for each administration group). The thickness of the auricle was measured before applying the imiquimod cream (Day 0) and about 24 hours after the final administration of each evaluation substance (Day 1 to Day 4), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation. It should be noted that Day 0 was the day when the application of imiquimod cream started.

[0070] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 1 . The ** in the figure indicates a significant difference relative to the 0.5% MC group (**P<0.01). Compared with 0.5% MC, 3 mg / kg body weight of MSP (5-HT4 receptor agonist) (Example of the present invention) significantly inhibited auricular hypertrophy, similar to 10 mg / kg body weight of APR (positive control). On the other hand, 3 mg / kg body weight of RZT (5-HT1 receptor agonist) (Comparative Example), 3 mg / kg body weight of TDS (5-HT1 receptor agonist) (Comparative Example) and 3 mg / kg body weight of LCS (5-HT2 receptor agonist) (Comparative Example) did not inhibit auricular hypertrophy.

[0071] [Test Example 2] Dose responsiveness of MSP (5-HT4 receptor agonist)

[0072] In order to confirm the effect (dose responsiveness) of MSP (5-HT receptor 4 agonist) on dermatitis in psoriasis model mice, the following test was performed.

[0073] Psoriasis model mice were prepared by the same method as in Experimental Example 1, and the vehicle (0.5% MC), 3 mg / kg body weight MSP, 30 mg / kg body weight MSP and 10 mg / kg body weight APR (positive control) were orally administered at 10 mL / kg body weight (Day 0 to Day 3) (n=6 in each administration group), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation.

[0074] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 2 . Respectively, ** in the figure indicates a significant difference when two groups are tested on the 0.5% MC group (**P<0.01), and ## indicates a significant difference when multiple groups are tested on the 0.5% MC group (##P<0.01). It is suggested that: compared with 0.5% MC, 3 mg / kg body weight MSP (an example of the present invention) and 30 mg / kg body weight MSP (an example of the present invention) both significantly inhibit auricular hypertrophy in a dose-dependent manner, and the inhibitory effect is equivalent to that of 10 mg / kg body weight APR (positive control).

[0075] [Test Example 3] Dose responsiveness of PCP and VRG (5-HT4 receptor agonist)

[0076] The following test was conducted to confirm the effects (dose responsiveness) of PCP and VRG (5-HT receptor 4 agonist) on dermatitis in psoriasis model mice. MSP (5-HT receptor 4 agonist) whose overdose responsiveness was confirmed in the above-mentioned Test Example 2 was also tested.

[0077] Psoriasis model mice were prepared by the same method as in Experimental Example 1, and the excipient (0.5% MC), 3 mg / kg body weight MSP, 3 mg / kg body weight PCP, 10 mg / kg body weight PCP, 30 mg / kg body weight PCP, 3 mg / kg body weight VRG, 10 mg / kg body weight VRG, 30 mg / kg body weight VRG and 10 mg / kg body weight APR (positive control) were orally administered at 10 mL / kg (Day 0 to Day 3) (n=6 in each administration group), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation.

[0078] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 3 . In the figure, ** indicates a significant difference when two groups are tested on the 0.5% MC group (**P<0.01), and ## indicates a significant difference when multiple groups are tested on the 0.5% MC group (##P<0.01). Compared with 0.5% MC, PCP (Example of the present invention) and VRG (Example of the present invention) significantly inhibited auricular hypertrophy at any dosage, similar to 10 mg / kg body weight APR (positive control) and 3 mg / kg body weight MSP (Example of the present invention).

[0079] [Test Example 4] Effects of 5-HT4 receptor agonists (CNP and CBP)

[0080] The following test was conducted to confirm the effects of CNP and CBP (5-HT receptor 4 agonist) on dermatitis in psoriasis model mice. MSP and VRG (5-HT receptor 4 agonist) which were confirmed to be overdose-responsive in the above-mentioned Test Examples 2 and 3 were also tested.

[0081] Psoriasis model mice were prepared by the same method as in Experimental Example 1, and the vehicle (0.5% MC), 30 mg / kg body weight MSP, 30 mg / kg body weight CNP, 30 mg / kg body weight VRG, 30 mg / kg body weight CBP, and 10 mg / kg body weight APR (positive control) were orally administered at 10 mL / kg body weight (Day 0 to Day 3) (n=6 in each administration group), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation.

[0082] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 4 . The * and ** in the figure indicate significant differences for the 0.5% MC group (*P<0.05, **P<0.01). Compared with 0.5% MC, 30 mg / kg body weight MSP (an example of the present invention), 30 mg / kg body weight CNP (an example of the present invention), 30 mg / kg body weight VRG (an example of the present invention), and 30 mg / kg body weight CBP (an example of the present invention) all significantly inhibited auricular hypertrophy, similarly to 10 mg / kg body weight APR (positive control).

[0083] [Test Example 5] Effects of 5-HT4 receptor agonists (CSP and TGR)

[0084] The following test was conducted to confirm the effects of CSP and TGR (5-HT receptor 4 agonist) on dermatitis in psoriasis model mice. PCP (5-HT receptor 4 agonist), which was confirmed to have overdose responsiveness in the above-mentioned Test Example 3, was also tested.

[0085] Psoriasis model mice were prepared by the same method as in Experimental Example 1, and the vehicle (0.5% MC), 30 mg / kg body weight PCP, 30 mg / kg body weight CSP, 30 mg / kg body weight TGR and 10 mg / kg body weight APR (positive control) were orally administered at 10 mL / kg body weight (Day 0 to Day 3) (n=6 in each administration group), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation.

[0086] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 5. The ** in the figure indicates a significant difference with respect to the 0.5% MC group (**P<0.01). Compared with 0.5% MC, similarly to 10 mg / kg body weight APR (positive control), 30 mg / kg body weight PCP (an example of the present invention), 30 mg / kg body weight CSP (an example of the present invention), and 30 mg / kg body weight TGR (an example of the present invention) all significantly inhibited auricular hypertrophy.

[0087] [Test Example 6] Effects of 5-HT4 receptor agonists (FCT, UMP, RLP and RZP)

[0088] In order to confirm the effects of FCT, UMP, RLP, and RZP (5-HT receptor 4 agonist) on dermatitis in psoriasis model mice, the following test was performed.

[0089] Psoriasis model mice were prepared by the same method as in Experimental Example 1, and the excipient (0.5% MC), 30 mg / kg body weight FCT, 30 mg / kg body weight UMP, 30 mg / kg body weight RLP, 30 mg / kg body weight RZP, 30 mg / kg body weight MSP and 10 mg / kg body weight APR (positive control) were orally administered at 10 mL / kg body weight (Day 0 to Day 3) (n=6 in each administration group), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation.

[0090] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 6 . The * and ** in the figure indicate significant differences when the two groups were tested on the 0.5% MC group (*P<0.05, **P<0.01). Compared with 0.5% MC, 30 mg / kg body weight FCT (Example of the present invention), 30 mg / kg body weight UMP (Example of the present invention), 30 mg / kg body weight RLP (Example of the present invention), and 30 mg / kg body weight RZP (Example of the present invention) all significantly inhibited auricular hypertrophy, as did 10 mg / kg body weight APR (positive control) and 30 mg / kg body weight MSP (Example of the present invention).

[0091] [Test Example 7] Effects of 5-HT4 receptor agonists (NRP, CJ-033466, RVP and E-3620)

[0092] The following test was performed to confirm the effects of NRP, CJ-033466, RVP, and E-3620 (5-HT receptor 4 agonist) on dermatitis in psoriasis model mice.

[0093] Psoriasis model mice were prepared by the same method as in Experimental Example 1, and the excipient (0.5% MC), 30 mg / kg body weight NRP, 30 mg / kg body weight CJ-033466, 30 mg / kg body weight RVP, 30 mg / kg body weight E-3620, 30 mg / kg body weight MSP and 10 mg / kg body weight APR (positive control) were orally administered at 10 mL / kg body weight (Day 0 to Day 3) (n=6 for each administration group), and the difference in auricle thickness between Day 0 and Day 4 (auricle hypertrophy) was evaluated as the degree of inflammation.

[0094] The results (auricle hypertrophy (average value) of each medication group) are shown in Figure 7 . The ** in the figure indicates a significant difference when the two groups were tested on the 0.5% MC group (**P<0.01). Compared with 0.5% MC, 30 mg / kg body weight NRP (example of the present invention), 30 mg / kg body weight CJ-033466 (example of the present invention), 30 mg / kg body weight RVP (example of the present invention), and 30 mg / kg body weight E-3620 (example of the present invention) all significantly inhibited auricular hypertrophy, as did 10 mg / kg body weight APR (positive control) and 30 mg / kg body weight MSP (example of the present invention).

[0095] The results of the above Test Examples 1 to 7 suggest that 5-HT4 receptor agonists are effective in treating psoriasis.

[0096] Industrial Applicability

[0097] According to the present invention, a novel therapeutic or preventive agent for psoriasis can be provided.

[0098] This application is based on Japanese Patent Application No. 2022-106025, the contents of which are all included in this specification.

Claims

1. A therapeutic or preventive agent for psoriasis, comprising a serotonin 4 receptor agonist.

2. The preparation according to claim 1, wherein The serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

3. The preparation according to claim 1 or 2, which is for oral administration.

4. A method for treating or preventing psoriasis, comprising the step of administering an effective amount of a serotonin 4 receptor agonist to a subject.

5. The method according to claim 4, wherein: The serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

6. The method according to claim 4 or 5, wherein: The drug is administered orally.

7. A serotonin 4 receptor agonist for use in the treatment or prevention of psoriasis.

8. The serotonin 4 receptor agonist according to claim 7, wherein The serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

9. The serotonin 4 receptor agonist according to claim 7 or 8, which is used for oral administration.

10. Use of a serotonin 4 receptor agonist in the manufacture of a therapeutic or preventive agent for psoriasis.

11. The use according to claim 10, wherein The serotonin 4 receptor agonist is one or more selected from mosapride, prucalopride, velusetrag, tegaserod, cisapride, cinitapride, clebopride, felcisetrag, naronapride, usmarapride, relenopride, renzapride, CJ-033466, revexepride, E-3620, and pharmaceutically acceptable salts thereof.

12. The use according to claim 10 or 11, wherein The therapeutic or preventive agent for psoriasis is for oral administration.

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