JPS60146826A - Psychotropic drug - Google Patents

Abstract

PURPOSE:A psychotropic drug, containing stabilized prostaglandin E1 as an active constituent, and having very little side effects. CONSTITUTION:A psychotropic drug containing stabilized prostaglandin (PG) E1, e.g. clathrate compound of cyclodextrin, as an active constituent in combination with a general-purpose base. PGs have individual various pharmacological action, but wholly exhibit powerful action in a very small amount, and are synthesized from precursors in the respective tissues and repidly metabolized after action thereof Particularly, PGE1 (11,15-dihydroxy-9-ketoprost-13-enoic acid) is synthesized even in nervous cells, and controls the release of a neurotransmitter substance, e.g. dopamine, to a synaptic cleft in a suppressed manner and controls the sensitivity of receptors of the neurotransmitter, substance on the postsynaptic numbrane side.

Description

[Detailed description of the invention] Technical field This invention relates to antipsychotic drugs.

Back Starvation Technology With the advent of antipsychotic drugs in recent years, the treatment of endogenous psychoses including schizophrenia has undergone revolutionary changes. Examples of this psychotropic drug include chlorproazine and haloperidol. These are all blockers of the neurotransmitter dopamine, and have shown excellent effects on the hallucinatory and delusional states and excited states during the acute phase of schizophrenia, which are thought to be caused by excess dopamine. . However, these antipsychotic drugs are all substances that cannot be synthesized in vivo, and as a result of their administration, strong side effects such as general malaise, tremor in the fingers, thirst, constipation, and strong drowsiness occurred. In addition to these obvious side effects, long-term use can also cause a negative state due to the drug.
There is also concern that it may induce hypersensitivity of dopamine receptors, increasing reactivity to stress.

Purpose The purpose of this invention is to provide a psychotropic drug that has extremely few side effects.

Examples Prostaglandins (hereinafter referred to as PG) regulate various metabolic processes in almost every tissue in the body, including immunity, inflammatory responses, and gastrointestinal motility.

It has been attracting attention as it has been revealed that it is involved in hematopoiesis, O-sen function, etc. PG is a general term for compounds that are unsaturated fatty acids consisting of 20 carbon atoms and have a cyclopentane ring at the center of the carbon chain.

And, due to the structure of this cyclopentane ring, PGA (
β-hydroxyketone>, PGF (1°3-diol), PGA (β-unsaturated ketone), etc.
Furthermore, depending on the number of double bonds in the carbon chain, e.g. PGEI'
(number of unsaturated bonds is 1), PGE2 (number of unsaturated bonds is 2), etc. Although the pharmacological effects of each of these l) Gs are individually different, they all have strong effects in extremely small amounts;
In addition, it is synthesized from precursor substances in each tissue, acts on it, and is rapidly metabolized. In particular, PGE1 is (11
゜15-dezahydroxy-9-ketoprostarter 1
3-enoic acid) is also synthesized within nerve cells and inhibits the release of neurotransmitters, such as dopamine, into the synaptic cleft. It is also thought to regulate the sensitivity of

The inventor conducted basic research on platelets, which are considered a peripheral model of monoaminergic neurons in the central nervous system, and deduced that PGEI is deficient in schizophrenia. Focusing on the above-mentioned pharmacological effects of PGEI, we investigated its use as a psychotropic drug, particularly for introverted psychoses including schizophrenia, and found that remarkable effects could be obtained with extremely minor side effects. I was able to confirm this and complete this invention.

According to the present invention, PGEI is used as an active ingredient in its stabilized state (for example, as a cyclodextrin clathrate) in combination with a commonly used base. Due to its instability, parenteral administration is appropriate, but
It is not limited to this. Administering via a blood vessel does not require an arterial route; sufficient effects can be obtained by intravenous infusion as shown below. In short, any method by which PGEI acts on the brain may be used.

The table introduces cases to which the antipsychotic drug according to the present invention was applied. Cases 1 to 6 shown in this table did not use any conventional psychotropic mulberry or sedatives, and PGE1 (
The results of treatment with alprostadil α-cyclodextrin clathrate) are shown. P
GE1 was administered by continuous intravenous infusion once a day at doses ranging from 1 to 2,000 gamma depending on the disease state. Even in cases of depression, good results ranging from mildly effective to markedly effective were obtained within a short period of time. In addition, half of the side effects are non-existent, and even if they occur, they are extremely minor. Below, Cases 1 to 3 will be explained in more detail.

Case 1: 19-year-old boy with schizophrenia since 2 weeks ago: ``By adjusting the frequency to my own brain waves and electrocardiogram, I can manipulate my own thoughts, or conversely, control my own thoughts.When I see a beautiful woman, I jump.'' He complained of telepathic experiences (auditory hallucinations), such as ``I can hear him and his orders coming into my head.'' At the same time, he also stated that ``someone is invading my house with the aim of taking my life'' (paranoia of victimization), and he had trouble sleeping at night.There were no specific abnormalities upon examination, and his consciousness was clear. A diagnosis of schizophrenia was made.For three days from the day of the examination, the patient was observed without active drug treatment, but the auditory hallucinations became more and more severe.From the fourth day of illness, with the approval of the mother, ,1
Once a day, PGEI 100 gamma was dissolved in physiological saline, and continuous intravenous infusion was performed for 3 hours. Approximately 1 hour later, facial flushing was observed, but no other side effects were observed. After the second treatment, the nine voices that criticized or gave orders about his actions almost disappeared. During the infusion treatment on the 3rd day of treatment, the patient began to feel a little excited and became talkative. On the 7th day of treatment (the 10th day of illness), he said, ``The reason I was doing such strange things was because I was tired,'' and he began to understand his illness, and his family life was back to the healthy period before his illness. It hasn't changed. From the 12th day of illness, the patient was switched to conventional low-dose oral antipsychotic therapy, and the patient was followed up with no major changes in his condition.

Case 2: 31-year-old male with atypical mental illness After he proposed marriage to a woman he liked about two weeks ago and was rejected, he gradually became talkative. After staying up all night for three days to prepare tax documents, he became extremely talkative, and there was verbal abuse and violence at home, so he was hospitalized overnight. At the time of admission, he was talkative, incoherent, and confused. The content of the story suggested paranoia. He denied hallucinations. Even after being admitted to the hospital, she continued to scream loudly, get naked, and remain in a state of excitement. From the 5th day of illness, PGIF, 150 gamma, was dissolved in physiological saline and administered intravenously once daily over 3 hours. From around the fifth day of treatment, he began to calm down and his expression became calmer. Two weeks after the start of treatment, he was able to speak coherently and was able to recall and reflect on the situation at the time of his admission.

On the 24th day after the start of treatment, the patient became aware of the disease and almost went into remission. No noteworthy side effects were observed with the tree treatment, either subjectively or objectively.

Case 3: 28-year-old male with schizophrenia of 26Aa, had delusions of poisoning and had been hospitalized for 1 month. Even after Lee, I sometimes had delusions about relationships and persecution. Since returning from skiing a week ago, I have been having trouble sleeping, and my work efficiency has not improved, so I have started taking time off from work. He also showed his violent past to his family members, and it became clear that he was delusional about being poisoned.

Although his progress in hospitalization was monitored, he remained wary of his surroundings and continued to refuse to eat or take medication. From the 9th day of illness, PGEI 50gamma was dissolved in physiological saline 500111 and administered by continuous intravenous infusion over approximately 3 hours once a day. After one week of treatment, the patient became less wary of his surroundings, did not refuse to eat or take medication, and began to answer questions honestly (disappearance of delusions of poisoning).

Three weeks later, the auditory hallucinations telling me bad things about myself had almost completely disappeared, and my persecutory delusions had completely disappeared. The patient stated that he felt ``feeling depressed during the infusion,'' but no other side effects were observed.

Incidentally, the amount of PGE1 is not limited to the above example, and can be increased or decreased according to the condition of the patient.

Effects As described above, the antipsychotic drug according to the present invention has excellent effects in that it brings about symptom improvement with short-term use and has little to no side effects or very slight side effects.

Patent application Person: Hisashi Hisashi Tani Agent Patent attorney: 1) Kazuo Wakasugi, Commissioner of the Patent Office, Mr. Hironobu1, Indication of the case Patent application filed on December 30, 19882 Name of the invention: Antipsychotic drug 3. Relationship with the case of the person making the amendment: Patent applicant address: 23 Kano Oishi-cho, Gifu City Name: Kaitani Omuro 4 Address of agent: No. 2 Equipment, Hatazume-cho, Gifu City, 500 Japan <0582> 65-1810 (Representative) The entire text of Book III is amended as shown in the attached sheet.

Description 1: Title of the invention Antipsychotic drug Claim 1: An antipsychotic drug containing stabilized prostaglandin E1 as an active ingredient.

2. Treatment of endogenous psychosis including schizophrenia 11! An anti-psychotic drug according to claim 1 for use as a medicine.

3. Detailed description of the invention Technical field This invention relates to antipsychotic drugs.

BACKGROUND ART With the advent of antipsychotic drugs in recent years, the treatment of endogenous psychoses including schizophrenia has undergone revolutionary changes. Examples of such antipsychotic drugs include chlorpromacine and heperidol. All of these are m% mulberry of the neurotransmitter dopamine, and have a wonderful effect on the hallucinatory and delusional state and excited state during the acute stage of schizophrenia, which is estimated by JIP to be caused by an excess of dopamine. Indicated. However, all of these antipsychotic drugs are substances that cannot be synthesized in vivo, and as a result of their administration, strong side effects such as general malaise, tremor in the fingers, thirst, constipation, and strong drowsiness have occurred. In addition to these obvious side effects, long-term use can also cause a drug-induced gap state and induce hyperthermia of dopamine receptors, leading to serious side effects such as tardive dyskinesia. There are also concerns.

Purpose This invention aims to provide an antipsychotic drug with extremely few side effects.

Examples Prostaglandins (hereinafter referred to as PG) regulate various metabolic processes in almost every tissue in the body, including immunity, inflammatory responses, and gastric III tract motility.

It has been attracting attention as it has been revealed that it is involved in hematopoiesis and renal function. PG is a general term for compounds that are unsaturated fatty acids consisting of 20 carbon atoms and have a cyclopentane ring in the middle of the carbon chain.

And, due to the structure of this cyclopentane ring, PGA (
PGF (1°3-diol), PGA (β-unsaturated ketone), etc. Depending on the number of double bonds in the carbon chain, for example, PGE1
(Number of unsaturated bonds: 1), PGE2 (Number of unsaturated bonds: 2)
It is classified as such. Although the pharmacological effects of each of these PGs are individually different, they all have strong effects in extremely small amounts, and are synthesized from precursors in each tissue.
action and is rapidly metabolized. In particular, PGE1 is (11゜15-dihydroxy-9-ketoprostarter 13
-Enoic acid) is also synthesized within nerve cells,
It is thought that it inhibits the release of neurotransmitters, such as dopamine, into the synaptic cleft, and also regulates the sensitivity of receptors for the neurotransmitters on the postsynaptic side.

The inventor conducted basic research on platelets, which are considered to be a peripheral model of monoaminergic neurons in the central nervous system, and deduced that PGEI is deficient in schizophrenia. Focusing on the above-mentioned pharmacological effects of PGE1, we focused on antipsychotic drugs,
In particular, as a result of investigating its use as an antipsychotic drug for endogenous psychosis including schizophrenia, it was confirmed that remarkable effects can be obtained with extremely minor side effects, leading to the completion of this invention.

-According to the present invention, PGEI is present in its stabilized state (
For example, a cyclodextrin clathrate compound) is used as an active ingredient in combination with a general-purpose base. Due to its instability, parenteral administration is suitable as the administration method, but is not limited thereto. Administration via a blood vessel does not require an arterial route; sufficient effects can be obtained by continuous intravenous drip administration as described below. In short, any method by which PGE1 acts on the brain may be used.

The table introduces cases to which the antipsychotic drug according to the present invention was applied. Cases 1 to 6 shown in this table did not use conventional antipsychotic drugs or sedatives, and PGE1
(alprostadil α-cyclodextrin clathrate) results are shown below.

l) G E 1 was administered by continuous intravenous infusion once a day at a total dose of 50 to 200 gamma depending on the condition of the patient. In all cases, favorable results ranging from mildly effective to markedly effective were obtained within a short period of time.

In addition, half of the side effects are non-existent, and even if they occur, they are extremely minor. Below, Cases 1 to 3 will be explained in more detail.

Case 1: 19-year-old boy with schizophrenia 2 weeks ago: ``By adjusting the frequency to his own brain waves and electrocardiogram, he manipulates his own thoughts, or conversely, extracts his own thoughts. He complained of telepathic experiences (hallucinations), such as when he saw a beautiful woman, a command to jump on him came to his head.At the same time, he also said, ``There was someone breaking into my house aiming for my life.'' The patient had paranoia and had insomnia at night. Upon examination, there were no notable physical abnormalities and the patient was conscious, and a diagnosis of schizophrenia was made. The patient was followed up for 3 days from the day of the consultation without active drug treatment, but the auditory hallucinations became more and more severe. From the 4th day of illness, PGEI 100 gamma was dissolved in physiological saline and administered as a continuous intravenous infusion for 3 hours once a day with the mother's approval.

Approximately 1 hour later, facial flushing was observed, but no other side effects were observed. After the second treatment, the behavior of criticizing or ordering one's own actions almost disappeared. During the infusion treatment on the 3rd day of treatment, the patient began to feel a little excited and became talkative. On the 7th day of treatment (10th day of illness), he said, ``The reason I was saying such strange things was because I was tired,'' and he began to understand his illness, and his home and domestic life were in good health. It hasn't changed since then. From the 12th day of illness, the patient was switched to oral therapy with a small amount of conventional antipsychotic drugs, and the patient's progress was observed without any major changes in his condition.

Example 2: 31-year-old male with schizophrenia After he proposed marriage to a woman he liked about two weeks ago and was turned down, he gradually became more talkative. After staying up all night for three days to prepare tax documents, he became extremely talkative, and there were abusive language and violence in the house, so he was hospitalized overnight. At the time of admission, he was talkative, incoherent, and confused. The content of the story suggested damage and hypochondriac delusions. He denied hallucinations.

Even after being admitted to the hospital, she continued to scream loudly, get naked, and remain in a state of excitement. Fifth
From the day of illness, PGEI 50 gamma was dissolved in physiological saline and intravenously administered once daily for 3 hours.

From around the fifth day of treatment, he began to calm down and his expression became calmer. Two weeks after the start of treatment, he was able to speak coherently and was able to recall the situation at the time of his hospitalization. Treatment start 2
On the fourth day, the patient became aware of his illness and almost went into remission. No noteworthy side effects were observed in this treatment, either subjectively or objectively.

Case 3: 28-year-old male, schizophrenia At the age of 26, he had delusions of poisoning and was hospitalized for one month.

Even after that, I sometimes had delusions about relationships and persecution. Since returning from skiing a week ago, I have been having trouble sleeping, and my work efficiency has not improved, so I have started taking time off from work. He also spoke violently to his family members, and it became clear that he was delusional about being poisoned.

Despite monitoring his progress during hospitalization, he remains wary of his surroundings and continues to refuse to eat or take medication. From the 9th day of illness, PGE150 gamma was dissolved in 500 IIL of physiological saline and administered intravenously for about 3 hours once a day. After one week of treatment, the patient became less wary of his surroundings, did not refuse to eat or refuse to eat, and began to answer questions honestly (disappearance of delusions of poisoning). 3
After 31 hours, the auditory hallucinations that told me bad things about myself had almost completely disappeared, and the persecutory delusions had completely disappeared. The patient stated that he felt ``feeling depressed during the infusion,'' but no other side effects were observed.

Incidentally, the amount of PGE'l is not limited to the above example, and can be increased or decreased according to the condition of the patient.

Effects As described above, the antipsychotic drug according to the present invention has an excellent effect in that it can improve psychotic symptoms with short-term use and has almost no side effects or only very slight side effects.

Patent Application Person: Hisashi Tani Agent Patent Attorney On 1) Hakusen Voluntary Procedure Light 11 Official Book 1982 , Name of the invention: Antipsychotic drug 3. Relationship with the person making the amendment: Patent applicant address: 23, Oishi-cho, Kano, Gifu City Name: Hisaru Kaitani: 4, Address of agent: 2-6, Hatazume-cho, Gifu-shi, 500 Japan , Contents of the amendment (1) The description of rGAJ in the second line of page 3 of the amended Meishosho e, voluntary procedure amendment dated November 20, 1984,
Correction with l'GEJ (2) The description of "3-diol" in the third line of the third column is corrected to "3-diol."

(3) [15-keto prostarta] on page 3, line 11
The description has been corrected to [15-dihydroxy-9-ketoprosta].

Claims (1)

[Claims] 1. The antipsychotic drug according to claim 1, which is used with stabilized prostaglandin E1.