JP2015074607A - Prevention of involuntary movement and/or therapeutic composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a prevention and/or a therapeutic composition of involuntary movement, particularly to provide a prevention and/or a therapeutic composition of dystonia.SOLUTION: It is confirmed that tardive dystonia can be improved by administering pramipexole hydrochloride hydrate which is a dopamine D2/D3 receptor agonist to patients developing tardive dystonia which causes involuntary movement, and thereby the prevention and/or the therapeutic composition (particularly, the prevention and/or the therapeutic composition of dystonia) of involuntary movement of the invention is completed.

Description

  The present invention relates to a composition for preventing and / or treating involuntary movements, in particular, a composition for preventing and / or treating dystonia.

(Involuntary movement)
Involuntary movement is a general term for movement that appears independently of intention or against intention. Even in healthy people, it is seen depending on the situation and may occur psychologically. It occurs in any disorder of the motor function control system of the central nervous system, but clinically it often appears as extrapyramidal symptoms including chorea.

(Dystonia)
Dystonia is a general term for a state in which various involuntary movements occur due to abnormal muscle tension. Dystonia is roughly classified into systemic dystonia in which the muscles of the whole body move abnormally and local dystonia due to abnormal muscle tone only in the region.
Furthermore, dystonia symptoms that appear under the influence of psychotropic drugs used for mental illness are called delayed dystonia.

(Treatment of dystonia)
As treatment of dystonia, benzazodiazepine-based drug administration, botulinum neurotoxin administration, anti-dopamine antagonist administration, anticholinergic administration, and administration of a stabilizer having a strong muscle relaxing action are known.
The active ingredient of the drug used in these therapeutic methods is completely different from the dopamine D2 / D3 receptor agonist which is the active ingredient of the involuntary movement prevention and / or treatment composition of the present invention.

There are also the following reports on the treatment of dystonia.
Patent Document 1 states that “a combined pharmaceutical composition comprising an activation-enhancing antibody against endothelial NO synthase and an activation-enhancing antibody against brain-specific protein S-100, as well as autonomic neurovascular dystonia (VVD) and symptoms thereof Its use for treating ". The active ingredient of the pharmaceutical composition described in this document is completely different from the dopamine D2 / D3 receptor agonist which is the active ingredient of the composition for preventing and / or treating involuntary movements of the present invention.
Patent Document 2 discloses “a prophylactic and / or therapeutic agent for a movement disorder having an adenosine A _2A receptor antagonistic action, which is a triazolopyrimidine derivative or a pharmacologically acceptable salt thereof”. The active ingredient of the pharmaceutical composition described in this document is completely different from the dopamine D2 / D3 receptor agonist which is the active ingredient of the composition for preventing and / or treating involuntary movements of the present invention.

  In addition, conventional dystonia treatment methods are less effective after long-term administration, and there are also problems of side effects.

Special table 2013-536174 gazette JP 2013-56911 A

  In this invention, it is providing the prevention and / or treatment composition of involuntary movement, especially the prevention and / or treatment composition of dystonia.

  The present inventors have confirmed that delayed dystonia can be improved by administering pramipexole hydrochloride hydrate, which is a dopamine D2 / D3 receptor agonist, to a patient with late-onset dystonia that develops involuntary movement. The composition for preventing and / or treating involuntary movement of the present invention (particularly, the composition for preventing and / or treating dystonia) was completed.

That is, the present invention is as follows.
1. A composition for preventing and / or treating involuntary movement comprising a dopamine D2 / D3 receptor agonist as an active ingredient.
2. 2. The preventive and / or therapeutic composition according to item 1 above, wherein the involuntary movement is dystonia.
3. 3. The preventive and / or therapeutic agent according to item 1 or 2, wherein the dopamine D2 / D3 receptor agonist is selected from any one or more of the following.
(1) Pramipexole hydrochloride hydrate or a pharmaceutically acceptable salt thereof (2) Pergolide mesylate salt or a pharmaceutically acceptable salt thereof (3) Cabergoline or a pharmaceutically acceptable salt thereof (4) Talipexol 3. Hydrochloride or pharmaceutically acceptable salt thereof (5) Rovinirole hydrochloride or pharmaceutically acceptable salt thereof A prophylactic and / or therapeutic composition for dystonia comprising pramipexole hydrochloride hydrate, a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient.
5. 5. The prevention and / or prevention according to item 4 above, wherein a daily dose of the pramipexole hydrochloride hydrate, a pharmaceutically acceptable salt thereof, or a solvate thereof is any of the following: Therapeutic agent.
(1) 0.1 mg to 0.7 mg
(2) 1.0mg to 1.9mg
6). A prophylactic and / or therapeutic composition for U-shape-type delayed dystonia, wherein the daily dose of pramipexole hydrochloride hydrate is 0.375 mg to 1.875 mg.
7). A prophylactic and / or therapeutic composition for tardive dystonia, wherein the daily dose of pramipexole hydrochloride hydrate is 0.375 mg to 0.75 mg.

  The novel involuntary movement prevention and / or treatment composition of the present invention has improved involuntary movement, particularly dystonia.

Changes in total ESRS score and ESRS-Dystonia score (Patient M)

(Involuntary movement prevention and / or treatment composition)
The composition for preventing and / or treating involuntary movements of the present invention (sometimes referred to as “the composition of the present invention”) contains at least an active ingredient as a dopamine D2 / D3 receptor agonist. The dopamine D2 / D3 receptor agonist means a dopamine D2 agonist and / or a dopamine D3 receptor agonist.
“Prevention” in the composition of the present invention refers to a patient who may cause involuntary movement, a patient who currently has no involuntary movement but has a past involuntary movement, etc. This means that the composition of the present invention is administered, but is not particularly limited.
“Treatment” in the composition of the present invention means, but is not limited to, alleviation, reduction, improvement, complete cure, etc. of involuntary movement of a patient who has developed involuntary movement.
Hereinafter, the composition for preventing and / or treating involuntary movement of the present invention will be described below.

(Involuntary movement)
The involuntary movements to be prevented or treated by administering the composition of the present invention can be listed as follows, but are not particularly limited. Preferably, dystonia, more preferably late-onset dystonia, is the target of prevention / treatment. The “dystonia” of the present invention includes late-onset dystonia.
(1) dystonia (2) tardive dystonia (3) dyskinesia (4) tardive dyskinesia (5) correa (6) balism (7) ataxia (8) akathisia (9) athetosis (10) tic (11) myoclonus

(Dopamine D2 / D3 receptor agonist)
The dopamine D2 / D3 receptor agonists contained as an active ingredient in the composition of the present invention can be listed as follows, but are not particularly limited as long as they are effective in preventing and treating involuntary movements. Pramipexole hydrochloride hydrate or a pharmaceutically acceptable salt thereof is preferred as the composition of the present invention.
(1) Pramipexole hydrochloride hydrate or a pharmaceutically acceptable salt thereof is marketed by Nippon Boehringer Ingelheim Co., Ltd. as a dopaminergic Parkinson's disease therapeutic agent or restless legs syndrome therapeutic agent.
(2) Pergolide mesylate or a pharmaceutically acceptable salt thereof As a dopamine D1, D2 agonist Parkinson's disease therapeutic agent, it is commercially available from Mylan et al.
(3) Cabergoline or a pharmaceutically acceptable salt thereof is commercially available from Pfizer Inc. as a dopamine agonist.
(4) Talipexol hydrochloride or a pharmaceutically acceptable salt thereof is sold by Nippon Boehringer Ingelheim Co., Ltd. as a treatment for Parkinson's disease.
(5) Rovinirole hydrochloride or a pharmaceutically acceptable salt thereof As a dopamine D2 receptor system agonist, it is sold by GlaxoSmithKline Co., Ltd.

(Composition of composition for preventing and / or treating involuntary movement)
In addition to the dopamine D2 / D3 receptor agonist, the composition of the present invention may contain other active ingredients that are effective against dystonia and other than the dopamine D2 / D3 receptor agonist.
In addition to these medicinal ingredients, an appropriate pharmaceutically acceptable carrier well known to those skilled in the art may be appropriately contained depending on the administration form. Pharmaceutically acceptable carriers include antioxidants, stabilizers, preservatives, flavoring agents, colorants, solubilizers, solubilizers, surfactants, emulsifiers, antifoaming agents, viscosity modifiers, gelling agents. , Absorption promoters, dispersants, excipients, pH adjusters and the like.

When the composition of the present invention is prepared as an injectable preparation, it is preferably in the form of a solution or suspension, and in the case of transmucosal administration such as nasal cavity and oral cavity, it is a powder, a drop, or an aerosol. The formulation form is preferred. In the case of rectal administration, a semi-solid preparation such as cream or suppository is preferable. All of these preparations should be prepared by any method known to those skilled in the pharmaceutical arts, as described, for example, in Remington's Pharmaceutical Sciences (Mac Publishing Company, Easton, PA, 1970). Can do.
Injectable preparations can contain, for example, plasma-derived proteins such as albumin, amino acids such as glycine, and sugars such as mannitol, and buffers, solubilizers, isotonic agents, and the like can be added as carriers. it can. In addition, when used as an aqueous preparation or a freeze-dried preparation, it is preferable to add a surfactant such as Tween ^{(registered trademark)} 80, Tween ^{(registered trademark)} 20 in order to prevent aggregation.
Furthermore, parenteral dosage forms other than injectable preparations may contain distilled water or physiological saline, polyalkylene glycols such as polyethylene glycol, oils of plant origin, hydrogenated naphthalene, and the like. Good. For example, preparations for rectal administration such as suppositories contain, for example, polyalkylene glycol, petrolatum, cacao oil and the like as common excipients. Vaginal preparations may contain absorption enhancers such as bile salts, ethylenediamine salts, and citrates. Inhalation formulations may be solid, may contain, for example, lactose as an excipient, and nasal drops may be water or oil solutions.

(Dosage and administration plan of involuntary movement prevention and / or treatment composition)
The exact dosage and dosing schedule of the composition of the present invention can be adjusted depending on the required amount for each individual treatment subject, the method of treatment, the degree of disease or necessity, and the like. The dosage can be specifically determined according to age, weight, general health condition, sex, diet, administration time, administration method, excretion rate, combination of drugs, patient's medical condition, etc. It may be determined in consideration of these factors.
When the composition of the present invention is administered to a patient who develops involuntary movement, the active ingredient contained in the composition contains an amount effective for reducing and / or preventing involuntary movement. Is preferred.
The daily dose varies depending on the patient's condition and body weight, the type of compound, the route of administration, and the like. For example, in the case of parenteral administration, the amount of active ingredient is about 0.01 to 1000 mg / person / day, preferably 0.1 It is desirably administered at about 500 mg / person / day, and in the case of oral administration at about 0.01-500 mg / person / day, preferably 0.1-100 mg / person / day.

(Prophylactic and / or therapeutic composition for involuntary movement comprising pramipexole hydrochloride hydrate as an active ingredient)
The preventive and / or therapeutic composition for involuntary movement comprising pramipexole hydrochloride hydrate of the present invention as an active ingredient is based on the following examples and the findings of the present inventors for patients with late-onset dystonia. The following appropriate daily dose has been newly found.
A minimal dosage of 0.1 to 0.7 mg, preferably 0.2 to 0.6 mg, more preferably about 0.375 mg can reduce phasic dystonia.
Medium dose of 1.0 to 1.95 mg, preferably 1.2 to 1.9 mg, more preferably about 1.8 mg, to improve dysonia of kinetic tension type, suppression of onset of continuous tone type dystonia, Furthermore, the onset of dyskinesia, which is a side effect, can be suppressed.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, this invention is not limited to this Example. Various modifications can be made without departing from the technical idea of the present invention.

(Confirmation of improvement in delayed dystonia by administration of dopamine D2 / D3 receptor agonist)
Pramipexole hydrochloride hydrate, a dopamine D2 / D3 receptor agonist, was administered to a patient diagnosed with delayed dystonia, an involuntary movement, to confirm improvement of delayed dystonia. Details are as follows. In addition, the improvement evaluation of dystonia is ESRS {Extrapyramidal Symptoms Rating Scale, evaluation scale of extrapyramidal symptoms: Reference: Guy Chouinarda, b, T, Howard C. Margolesea. Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophrenia Research 76 (2005) 247-265.} Was used.

(Patient M)
Patient M was treated for depression at a hospital in year X, and sulpiride (sulpiride: antipsychotic), levomepromazine (levomepromazine: antipsychotic), etc. were prescribed. Fluvoxamine (fluvoxamine: antidepressant) and imipramine (imipramine: antidepressant) seem to have been prescribed, but details are unknown.
From around January of X + 3, the neck began to move, causing pain in the neck and shoulders.
X + 4 February 10th, the first visit to our department for treatment-resistant depression and delayed dystonia. At the visit, lithium (lithium: mood stabilizer) 800mg, sulpride 100mg, seroquel (seroquel: antipsychotic) 75mg, biperiden (biperiden: anticholinergic) 2mg, paroxetine (paroxetine: antidepressant) 20mg, etc. are prescribed. It was. The patient was diagnosed with bipolar disorder and tardive dyskinesia. As a treatment policy, we treated mood disorders in our department, and delayed dystonia was treated with botulinum toxin type A (Botox). In addition, he was diagnosed with delayed dystonia of the neck due to antipsychotic drugs in neurology.
Trihexyphenidyl (trihexyphenidyl: an anticholinergic drug) was increased to 6 mg and clonazepam (clonazepam: a benzodiazepine and anxiolytic drug) to 1 mg, but there was no effect. The second injection of the botulinum toxin type A injection was performed, but the improvement was poor, and dysphagia appeared.
Since antidepressants and antipsychotics were discontinued and lithium 800 mg was able to stabilize the mood in the middle of August X + 4, psychiatric treatment was performed thereafter.

(1) X + 4, November 26 Late dystonia in the right cervical region was prominently seen, turning the head to the left and talking with both hands (ESRS 46 points). Formulation of 0.375 mg of Pramipexole sustained-release agent (pramipexole hydrochloride hydrate: dopamine D2 / D3 receptor agonist) was started.
(2) X + Nov. 29, 2004 Large gyration of the right neck improved and conversation was possible without restraining with both hands, but dystonia was still recognized (ESRS 27 points). Continuously, 0.375 mg of Pramipexole sustained-release agent was prescribed.
(3) December 10, X + 4 Dystonia was almost the same as the previous (ESRS 23 points). Therefore, the formulation of Pramipexole sustained release agent was increased to 0.75 mg.
(4) December 17, X + 4 Improvement was observed in dystonia (ESRS 16 points). Therefore, the formulation of Pramipexole sustained release agent was increased to 1.125 mg.
(5) X + January 7, dystonia was mild but improved further (ESRS 12 points). Therefore, the formulation of Pramipexole sustained release was increased to 1.5 mg.
(6) X + January 28, 2005 The turning motion was worsened (ESRS 34 points). Therefore, the formulation of Pramipexole sustained release agent was reduced to 1.125 mg.
(7) X + February 4, 5 Although dystonia showed an overall improvement, it was more severe than the previous dose (ESRS 27 points). In addition, the Pramipexole sustained-release agent was reduced to 0.75 mg and prescribed.
(8) X + 18 February 18, Dystonia improved slightly (ESRS 22 points). In addition, the formulation of Pramipexole sustained release was reduced to 0.375 mg.
(9) X + 25 Feb. 5 Dystonia showed further improvement (ESRS 11 points). Pramipexole sustained release agent was maintained at 0.375 mg.
(10) X + March 4, 5 Dystonia maintained its improved condition (ESRS 11 points). Pramipexole was formulated with sustained release agent 0.375 mg.
(11) X + March 18, 2005 Cervical dystonia worsened to an extent that could not be stopped without support with both hands (ESRS 26 points). Pramipexole sustained release agent was added again to 0.75 mg and prescribed.
(12) March 25, X + 5 Although improved from the previous time, there were fluctuations depending on the day (ESRS 22 points). Pramipexole was formulated with sustained release agent 0.75mg.
(13) X + April 8, 5 The dystonia, which is seizure-pulled, has disappeared, but when it became nervous, dystonia appeared (ESRS 19 points). Pramipexole was formulated with sustained release agent 0.75mg.
(14) X + April 25, 5 Symptoms such as shaking and tilting to the right were observed, the movement was supported by one hand, and the condition worsened slightly (ESRS 22 points). Pramipexole was formulated with sustained release agent 0.75mg.
(15) X + 6/6/6 Dystonia improved slightly (ESRS 19 points). Pramipexole sustained-release agent was further increased and prescribed at 1.125 mg.
(16) X + June 20, dystonia improved (ESRS 14 points). Pramipexole sustained release agent was increased and prescribed at 1.5 mg.
(17) X + June 27, dystonia improved (ESRS 6 points). Patient M's awareness was unchanged. Pramipexole sustained release agent was formulated at 1.5 mg.
(18) 18 July X + 5 Dystonia remained unchanged (ESRS 6 points). Pramipexole sustained-release agent was prescribed to 1.875 mg.
(19) X + 8 Aug. 8, tilted slightly to the right but remained unchanged (ESRS 6 points). Pramipexole sustained release agent was maintained at 1.875 mg.
(20) August 29, X + 5 It may be aggravated by mental tension, but the improvement was maintained at the time of examination (ESRS 6 points). Pramipexole was formulated with sustained release agent 1.875 mg.

(Confirmation of improvement in dystonia in patient M)
The administration schedule of the pramipexole hydrochloride hydrate (Pramipexole sustained release agent), the total ESRS score, and the ESRS-Dystonia score are shown in Table 1 below. Furthermore, the transition of the total ESRS score and ESRS-Dystonia score is shown in FIG.
As apparent from Table 1 and FIG. 1 below, administration of pramipexole hydrochloride hydrate decreased the ESRS score. That is, it was confirmed that extrapyramidal symptoms, particularly delayed dystonia, were improved.
More specifically, pramipexole hydrochloride hydrate improved delayed dystonia in an initial dose-dependent manner, but then worsened at 1.5 mg and improved with weight loss. However, since it worsened again, it was improved again by increasing the dose and then maintained at 1.875 mg. Although compliance is based on the patient's declaration, it is possible to obtain a U-shape-type delayed dystonia-improving effect that manifests an effect from a small amount and then deteriorates transiently by increasing the dose, but can be improved by further increasing the dose. It was.

(Patient N)
The diagnosis name of this patient N was schizophrenia emotional disorder and tardive dyskinesia. Involuntary movements appeared after long-term use of antipsychotic drugs, especially involuntary movements worsened by slight stress, and symptoms were not improved even after reducing antipsychotic drugs, so late-onset dystonia was diagnosed . Details are as follows.

(1) In May 1996, the dosage was increased to 18 mg using HPD (haloperidol: antipsychotic) for 2-3 weeks. At the time of the increase, acute dystonia appeared. Therefore, RIS (risperidone: an antipsychotic drug) was changed to 4 mg, and then maintained at 3 to 4 mg for about 10 years, and delayed dystonia appeared in the state of RIS 4 mg.
(2) From around March 2010, involuntary movement of late-onset dystonia, left torsion of the neck, torsion involving the trunk of the neck from the left upper limb, and closed eyes due to tension of the ocular muscles appeared.
When Mirapex ^{(registered trademark)} (pramipexole hydrochloride hydrate: dopamine D2 / D3 receptor agonist) was increased to 0.375 mg, each of the above symptoms was mildly reduced. However, it was a symptom that could not eat yet. In addition, an increase of 0.75 mg improved torsion of the left upper limb and closed eyes due to the tension of the ocular muscles.

(Confirmation of improvement in dystonia in patient N)
Administration schedule of the above pramipexole hydrochloride hydrate, total ESRS score, ESRS-Dystonia score, PANSS (Positive and Negative Syndrome Scale) total score and GAF (Global Assessment of Functioning: daily life and social life) Table 2 below shows the scores.
As is clear from Table 2 below, administration of pramipexole hydrochloride hydrate decreased the ESRS score and ESRS-Dystonia score. That is, it was confirmed that extrapyramidal symptoms, particularly dystonia, were improved.
There was no change in score for PANSS. That is, administration of pramipexole hydrochloride hydrate did not affect or improve schizophrenia.
Regarding GAF, the score increased. That is, the increase in schizophrenia symptoms despite no change has greatly improved the quality of life due to the improvement of dystonia.
As described above, extrapyramidal symptoms and dystonia were improved by administration of pramipexole hydrochloride hydrate. However, there was no change in schizophrenia. That is, since only dystonia, which is a side effect of the therapeutic drug for schizophrenia, was improved, pramipexole hydrochloride hydrate improved dystonia.

(General comments)
Based on the results of the above Example 1 and the present inventors' knowledge, the present inventors obtained the number of presynaptic D2 receptors by long-term administration of an antipsychotic drug (dopamine D2 receptor antagonist or dopamine D2 / D3 antagonist). And the number of D3 receptors is increased, and this increase is considered to cause late dystonia.
And, involuntary movements by administration of dopamine D2 / D3 receptor agonists, especially the improvement of delayed dystonia, are exerted by acting on presynaptic D2 and D3 receptors, and the mechanism and slow development of delayed dystonia The dose-dependent effects of the released dopamine D2 receptor agonist are considered to be:

(Delayed dystonia mechanism)
In late-onset dystonia, local muscles contract temporarily when trying to maintain stress and posture, and the type (phasic type, phasic tension type) repeats, and local muscles are persistent. It can be broadly divided into types that maintain tension and continue to be twisted (tonic type). The presynaptic (pre-synaptic) dopamine D2 and D3 receptors have higher binding affinity to dopamine than the post-synaptic (post-synaptic) D2 and D3 receptors. Therefore, the released dopamine binds to the presynaptic D2 and D3 receptors and suppresses and stops dopamine release. If the number of presynaptic D2 and D3 receptors is increased, the exercise associated with dopamine release is over-suppressed at once, but dopamine is released again due to the lack of dopamine, resulting in over-suppression of exercise. Shows phasic tension type. On the other hand, when the number of dopamine D2 and D3 receptors in the presynapse is excessive, release is suppressed even by the amount of dopamine that is always present in the synaptic cleft, resulting in tension-sustained dystonia.

(Dose-dependent effect of sustained-release dopamine D2 receptor agonist)
1. (Very low dose)
A very low dose of sustained-release dopamine D2 receptor agonists of a certain amount or less always binds to a small number of presynaptic D2 receptors, but hardly suppresses dopamine release via presynaptic D2 receptors. It is done. Therefore, if the affinity of the agonist for the D2 receptor is sufficiently high, since a certain amount of D2 receptor is already occupied by the agonist, the presynaptic D2 to which dopamine released by stress or the like can bind can be bound. The number of receptors decreases. As a result, the rapid release suppression that occurs after the release of dopamine is reduced, and the kinetic dystonia is reduced.
The extremely low dose is about 0.375 mg per day.
2. (Low dose)
When the dose of the sustained release dopamine D2 receptor agonist is further increased from the above “1”, mild dopamine release is suppressed via the dopamine D2 receptor. If dopamine is released due to stress or the like at this time, the rapid release suppression caused by the transient increase in dopamine and the release suppression caused by the agonist interact with each other, and the dysonia of the kinetic tension type is again Getting worse.
The low dose is about 0.75 mg per day.
3. (Medium dose)
When the dose of sustained-release dopamine D2 receptor agonist is further increased from “2” above, dopamine is released by stress, etc., by continuously binding to a relatively large amount of dopamine D2 receptor and suppressing dopamine release. The amount is also reduced. As a result, dystonia with kinetic tension improves.
The medium dose is about 1.5 mg per day.
4). (High dose)
If the dose of the sustained-release dopamine D2 receptor agonist is increased from the above “3”, the dopamine release amount is always excessively suppressed due to excessive occupation of the presynaptic D2 receptor, and stress Since the amount of dopamine released in the same manner is small, sustained tension type dystonia occurs.
The high dose is about 2.000 mg per day.
5. (Extreme dose)
The dose of sustained-release dopamine D2 receptor agonist is excessively large, that is, administration in the treatment of Parkinson's disease starts a response when stimulating the post-synaptic D2 receptor. In this case, since the number of post-synaptic D2 receptors may be excessive in people with late-onset dystonia, dyskinesia occurs in such cases.

(Slow release dopamine D2 / D3 receptor agonist)
For D2 / D3 receptor agonists such as Pramipexole et al., It can be considered that a dose-dependent action via the D3 receptor also occurs at the same time.
In this case, the receptor through which the action occurs first depends on the high affinity of the drug for the D2 receptor and the high affinity for the D3 receptor. In the case of Pramipexole, the affinity for the D3 receptor is about 60 times that of the D2 receptor, and at extremely low doses, the effects mediated mainly by the D3 receptor appear mainly. It is done.

  The present invention can provide a novel preventive and / or therapeutic composition for involuntary movement, particularly a dystonia preventive and / or therapeutic composition.

Claims (7)

A composition for preventing and / or treating involuntary movement comprising a dopamine D2 / D3 receptor agonist as an active ingredient.
The prophylactic and / or therapeutic composition according to claim 1, wherein the involuntary movement is dystonia.
The preventive and / or therapeutic agent according to claim 1 or 2, wherein the dopamine D2 / D3 receptor agonist is selected from any one or more of the following.
(1) Pramipexole hydrochloride hydrate or a pharmaceutically acceptable salt thereof (2) Pergolide mesylate salt or a pharmaceutically acceptable salt thereof (3) Cabergoline or a pharmaceutically acceptable salt thereof (4) Talipexol Hydrochloride or pharmaceutically acceptable salt thereof (5) Rovinirole hydrochloride or pharmaceutically acceptable salt thereof
A prophylactic and / or therapeutic composition for dystonia comprising pramipexole hydrochloride hydrate, a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient.
The daily dose of the pramipexole hydrochloride hydrate, a pharmaceutically acceptable salt thereof, or a solvate thereof is any one of the following: Or a therapeutic agent.
(1) 0.1 mg to 0.7 mg
(2) 1.0mg to 1.9mg
A prophylactic and / or therapeutic composition for U-shape-type delayed dystonia, wherein the daily dose of pramipexole hydrochloride hydrate is 0.375 mg to 1.875 mg.
  A prophylactic and / or therapeutic composition for tardive dystonia, wherein the daily dose of pramipexole hydrochloride hydrate is 0.375 mg to 0.75 mg.