JPH11171786A - Psychotropic agent containing peptide as active ingredient - Google Patents
Psychotropic agent containing peptide as active ingredientInfo
- Publication number
- JPH11171786A JPH11171786A JP9362814A JP36281497A JPH11171786A JP H11171786 A JPH11171786 A JP H11171786A JP 9362814 A JP9362814 A JP 9362814A JP 36281497 A JP36281497 A JP 36281497A JP H11171786 A JPH11171786 A JP H11171786A
- Authority
- JP
- Japan
- Prior art keywords
- active ingredient
- peptide
- agent
- pglu
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明はペプチド又はそれら
の薬理学的に許容される塩を有効成分として含有する向
精神薬に関し、詳細には次の一般式（Ｉ）、 Ａ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−Ｂ （Ｉ） （式中，Ａは、ｐＧｌｕ又はＨを表し、そしてＢはＮＨ
2 又はＯＨを表す） で表されるペプチド又はそれらの薬理学的に許容される
塩を有効成分として含有する抗不安薬、並びにこのペプ
チド又はそれらの薬理学的に許容される塩を有効成分と
して含有する抗うつ薬に関する。TECHNICAL FIELD The present invention relates to a psychotropic drug containing a peptide or a pharmacologically acceptable salt thereof as an active ingredient, and more particularly, to the following general formula (I): A-Asn-Ser- Pro-Arg-Gly-B (I) wherein A represents pGlu or H, and B is NH
2 or OH) or an anxiolytic drug containing as an active ingredient a peptide represented by the formula or a pharmaceutically acceptable salt thereof, and the peptide or a pharmaceutically acceptable salt thereof as an active ingredient Related to antidepressants.
【０００２】[0002]
【従来の技術】抗うつ薬としては、古くはモノアミン酸
化酵素（ＭＡＯ）阻害薬、そしてアミトリプチリン、イ
ミプラミンなどの三環系抗うつ薬、ミアンセリン、マプ
ロチリンなどの四環系抗うつ薬などが開発され、最近で
はフルオキセチン、サ−トラリン、パロキセチンなどの
セロトニン再取り込み阻害剤（ＳＳＲＩ）が開発されて
きている。これら既存の抗うつ薬のうち、ＭＡＯ阻害薬
においては、肝障害、過度の興奮作用、中毒性精神異
常、不眠、起立性低血圧、めまい、耳鳴り、便秘などの
副作用が知られており、三環系抗うつ薬では頻度の高い
副作用として抗コリン作用からくるもので、口褐、頻
脈、起立性低血圧、めまい、眼調節障害などが知られて
いる。2. Description of the Related Art As antidepressants, monoamine oxidase (MAO) inhibitors, tricyclic antidepressants such as amitriptyline and imipramine, and tetracyclic antidepressants such as mianserin and maprotiline have been developed. Recently, serotonin reuptake inhibitors (SSRIs) such as fluoxetine, satraline and paroxetine have been developed. Among these existing antidepressants, MAO inhibitors are known to have side effects such as liver damage, excessive stimulant effects, toxic psychosis, insomnia, orthostatic hypotension, dizziness, tinnitus, and constipation. Frequent side effects of cyclic antidepressants are due to anticholinergic effects, and are known to be brownish brown, tachycardia, orthostatic hypotension, dizziness, dysregulation and the like.
【０００３】一方、抗不安薬としては、ジアゼパム、エ
チゾラム、ロフラゼブ酸エチル、クロチアゼパム、トフ
ィソパムなどのベンゾジアゼピン（ＢＺ）系とクエン酸
タンドスピロンなどの非ＢＺ系が知られている。このう
ちＢＺ系の抗不安薬の副作用としては、運動機能の抑
制、アルコールなどとの相互作用、認知機能への影響
（物忘れ）、筋弛緩作用、鎮静、傾眠、脱力感などが知
られている。従って、副作用の軽減された新規な抗うつ
薬、抗不安薬の開発が求められている。On the other hand, as anxiolytics, benzodiazepines (BZ) such as diazepam, etizolam, ethyl loflazebate, clothiazepam, tofisopam and non-BZs such as tandospirone citrate are known. Among these, the side effects of BZ anxiolytics include inhibition of motor function, interaction with alcohol and the like, influence on cognitive function (forgetfulness), muscle relaxation, sedation, somnolence, weakness, and the like. . Therefore, there is a need for the development of new antidepressants and anxiolytics with reduced side effects.
【０００４】ところで、次式（II）、 ｐＧｌｕ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 （II） で表されるペプチド及びその薬理学的に許容される塩は
学習行動促進作用もしくは学習障害改善作用を有し、抗
痴呆剤として有用であることは知られている。（特公平
８−２６０６９） そして上記式（II）で表されるペプチド及びその薬理学
的に許容される塩、並びにアルギニン・バソプレシン
（ＡＶＰ（１−９））及びその脳内活性代謝物である
［ｐＧｌｕ4 ，Ｃｙｔ6 ］ＡＶＰ（４−９）について、
これらのペプチド又はその薬理学的に許容される塩と抗
不安作用や抗うつ作用との関係について明確に述べられ
た文献等は知られていない。Incidentally, a peptide represented by the following formula (II), pGlu-Asn-Ser-Pro-Arg-Gly-NH 2 (II) and a pharmacologically acceptable salt thereof have a learning-promoting action or learning action. It is known that it has a disorder improving effect and is useful as an anti-dementia agent. (Japanese Patent Publication No. 8-26069) and a peptide represented by the above formula (II) and a pharmacologically acceptable salt thereof, and arginine vasopressin (AVP (1-9)) and an active metabolite in the brain. [PGlu 4 , Cyt 6 ] AVP (4-9)
There is no known literature or the like which clearly describes the relationship between these peptides or pharmacologically acceptable salts thereof and anxiolytic and antidepressant effects.
【０００５】[0005]
【発明が解決しようとする課題】本発明者らは、上記式
（II）で表されるペプチド及びその薬理学的に許容され
る塩に関する更なる薬理作用に関する研究を進めた結
果、従来の抗うつ薬、抗不安薬とは構造が全く異なるに
もかかわらず上記のペプチド及びその薬理学的に許容さ
れる塩が抗不安作用、抗うつ作用といった向精神作用を
有することを見いだし本発明を完成した。DISCLOSURE OF THE INVENTION The present inventors have conducted a study on the further pharmacological action of the peptide represented by the above formula (II) and a pharmacologically acceptable salt thereof. Despite the fact that the above-mentioned peptide and its pharmacologically acceptable salts have psychoactive effects such as anxiolytic and antidepressant effects, the present invention has been completed despite the fact that the structure is completely different from that of depressants and anxiolytics. did.
【０００６】[0006]
【課題を解決するための手段】即ち、本発明は次の一般
式（Ｉ）、 Ａ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−Ｂ （Ｉ） （式中、ＡはｐＧｌｕ又はＨを表し、そしてＢはＮＨ2
又はＯＨを表す） で表されるペプチド又はそれらの薬理学的に許容される
塩を有効成分として含有する抗不安薬に関する。また、
本発明は次式（II）、 ｐＧｌｕ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 （II） で表されるペプチド又はその薬理学的に許容される塩を
有効成分として含有する抗不安薬に関する。また、本発
明は次の一般式（Ｉ）、 Ａ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−Ｂ （Ｉ） （式中，Ａは、ｐＧｌｕ又はＨを表し、そしてＢはＮＨ
2 又はＯＨを表す） で表されるペプチド又はそれらの薬理学的に許容される
塩を有効成分として含有する抗うつ薬に関する。さらに
また、本発明は次式（II）、 ｐＧｌｕ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 （II） で表されるペプチド又はその薬理学的に許容される塩を
有効成分として含有する抗うつ薬に関する。That is, the present invention provides the following general formula (I): A-Asn-Ser-Pro-Arg-Gly-B (I) (wherein A represents pGlu or H; And B is NH 2
Or OH) or a pharmacologically acceptable salt thereof as an active ingredient. Also,
The present invention provides an anxiolytic comprising a peptide represented by the following formula (II): pGlu-Asn-Ser-Pro-Arg-Gly-NH 2 (II) or a pharmacologically acceptable salt thereof as an active ingredient. About. Further, the present invention provides the following general formula (I): A-Asn-Ser-Pro-Arg-Gly-B (I) (where A represents pGlu or H, and B represents NH
2 or OH) or a pharmacologically acceptable salt thereof as an active ingredient. Furthermore, the present invention contains a peptide represented by the following formula (II), pGlu-Asn-Ser-Pro-Arg-Gly-NH 2 (II) or a pharmacologically acceptable salt thereof as an active ingredient. Regarding antidepressants.
【０００７】本明細書においてはアミノ酸を下記の略号
で示す。又、各アミノ酸の光学配置はＬ−型である。 ｐＧｌｕ：ピログルタミン酸 Ａｓｎ：アスパラギン Ｓｅｒ：セリン Ｐｒｏ：プロリン Ａｒｇ：アルギニン Ｇｌｙ：グリシン[0007] In the present specification, amino acids are represented by the following abbreviations. The optical configuration of each amino acid is L-type. pGlu: pyroglutamic acid Asn: asparagine Ser: serine Pro: proline Arg: arginine Gly: glycine
【０００８】本発明の有効成分である上記一般式（Ｉ）
で表されるペプチド及びそれらの薬理学的に許容される
塩は、特公平８−２６０６９記載の方法等により得るこ
とができる。上記一般式（Ｉ）で表されるペプチドの薬
理学的に許容される塩としては、酸付加塩及び塩基性塩
が挙げられ、酸付加塩としては、たとえば酢酸、塩酸、
クエン酸、メタンスルホン酸等との塩、そして塩基性塩
としては、ナトリウム塩、カリウム塩、トリエチルアミ
ン塩等が挙げられる。The above-mentioned general formula (I) which is an active ingredient of the present invention
And the pharmacologically acceptable salts thereof can be obtained by the method described in JP-B-8-26069 or the like. The pharmacologically acceptable salts of the peptide represented by the above general formula (I) include acid addition salts and basic salts. Examples of the acid addition salts include acetic acid, hydrochloric acid,
Salts with citric acid, methanesulfonic acid and the like, and basic salts include sodium salt, potassium salt and triethylamine salt.
【０００９】次に、上記一般式（Ｉ）で表されるペプチ
ド又はそれらの薬理学的に許容される塩を有効成分とし
て含有する製剤が、抗不安薬あるいは抗うつ薬として有
用であることは以下の薬理実験から明らかになった。ま
ず、本発明の有効成分である次式（II）、 ｐＧｌｕ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−
ＮＨ2 で表されるペプチドの酢酸塩の抗不安作用は、ｄｄＹ系
マウスを用いた高架式十字型迷路法により明らかになっ
た。即ち、上記の式（II）で表されるペプチドの酢酸塩
が公知の抗不安薬であるジアゼパムと比較して１／１，
０００〜１／５，０００の用量で抗不安作用を示し、上
記の式（II）で表されるペプチド又はその薬理学的に許
容される塩を含む本発明製剤が抗不安薬として有用であ
ることが判明した。Next, it is known that a preparation containing the peptide represented by the above general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient is useful as an anxiolytic or antidepressant. The following pharmacological experiments revealed this. First, an active ingredient of the present invention represented by the following formula (II): pGlu-Asn-Ser-Pro-Arg-Gly-
The anxiolytic effect of the acetate of the peptide represented by NH 2 was revealed by an elevated cross maze method using ddY mice. That is, the acetate of the peptide represented by the above formula (II) is 1/1, compared with diazepam which is a known anxiolytic drug.
The drug of the present invention which shows an anxiolytic effect at a dose of 000 to 1 / 5,000 and contains the peptide represented by the above formula (II) or a pharmaceutically acceptable salt thereof is useful as an anxiolytic. It has been found.
【００１０】また、本発明の有効成分である上記の式
（II）で表されるペプチドの酢酸塩の抗うつ作用は、ｄ
ｄＹ系マウスを用いた強制水泳法により明らかになっ
た。即ち、上記の式（II）で表されるペプチドの酢酸塩
は公知の抗うつ薬であるアミトリプチリンと比較して１
／５００，０００の用量でより持続性をもった抗うつ作
用を示し、上記の式（II）で表されるペプチド又はその
薬理学的に許容される塩を含む本発明製剤が抗うつ薬と
して有用であることが判明した。The antidepressant action of the acetate of the peptide represented by the above formula (II), which is an active ingredient of the present invention, is represented by d
It was revealed by forced swimming using dY mice. That is, the acetate of the peptide represented by the above formula (II) is 1% less than amitriptyline, which is a known antidepressant.
/ 500,000 shows a more prolonged antidepressant action, and the preparation of the present invention containing the peptide represented by the above formula (II) or a pharmacologically acceptable salt thereof is useful as an antidepressant. It turned out to be useful.
【００１１】本発明の有効成分である上記一般式（Ｉ）
で表されるペプチド又はそれらの薬理学的に許容される
塩は一般的に非経口的に投与（例：静脈又は皮下注射、
脳室内又は脊髄腔内投与、経鼻投与、直腸投与）される
が、場合によっては経口投与されることもある。剤型と
しては、例えば、注射剤、点鼻剤、坐剤、錠剤、散剤等
が挙げられる。非経口投与製剤で注射剤の場合、注射用
蒸留水、生理食塩水、リンゲル液等を用いて調整するこ
とができる。またマンニトール、ソルビトール等の添加
剤を添加して凍結乾燥アンプルとして使用時に溶解する
こともできる。The above-mentioned general formula (I) which is an active ingredient of the present invention.
The peptide represented by or a pharmaceutically acceptable salt thereof is generally administered parenterally (eg, intravenous or subcutaneous injection,
Intraventricular or intrathecal administration, nasal administration, rectal administration), and in some cases, oral administration. Dosage forms include, for example, injections, nasal drops, suppositories, tablets, powders and the like. In the case of parenteral administration preparations and injections, the preparation can be prepared using distilled water for injection, physiological saline, Ringer's solution and the like. Additives such as mannitol and sorbitol can be added and dissolved when used as a lyophilized ampoule.
【００１２】本発明の有効成分である上記一般式（Ｉ）
で表されるペプチド又はそれらの薬理学的に許容される
塩を成人に投与する場合、一般には１日当たり０．１ｎ
ｇ〜１ｍｇである。非経口投与及び経鼻投与では、０．
１ｎｇ〜１００μｇが好ましく、また経口投与及び直腸
投与では非経口投与の１０〜１００倍投与することが好
ましいが、年齢、人種、症状等により増減することがで
きる。The above-mentioned general formula (I) which is an active ingredient of the present invention.
When the peptide represented by the formula or a pharmaceutically acceptable salt thereof is administered to an adult, it is generally 0.1 n / day
g to 1 mg. For parenteral and nasal administration, 0.1 mg.
The dose is preferably 1 ng to 100 μg, and in oral administration and rectal administration, it is preferably 10 to 100 times that of parenteral administration, but it may be increased or decreased depending on age, race, symptoms and the like.
【００１３】[0013]
【実施例】以下、実施例に基づいて本発明をさらに詳し
く説明するが、本発明はこれらに限られるものではな
い。 実施例１ 製剤例（注射剤） 注射用蒸留水１００ｍｌ中に、ｐＧｌｕ−Ａｓｎ−Ｓｅ
ｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の酢酸塩０．１ｍ
ｇ、および塩化ナトリウム０．９ｇを含有させ、ｐＨを
水酸化ナトリウムで６．０〜８．０に調節した水溶液を
調整した。これを細菌濾過後１ｍｌアンプルに充填、閉
加熱滅菌して注射剤を製造した。The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. Example 1 Formulation Example (Injection) pGlu-Asn-Se in 100 ml of distilled water for injection
r-Pro-Arg-Gly-NH 2 acetate 0.1 m
g and 0.9 g of sodium chloride, and the pH of the aqueous solution was adjusted to 6.0 to 8.0 with sodium hydroxide. This was filtered into bacteria, filled into 1 ml ampules, closed and sterilized by heating to produce an injection.
【００１４】実施例２ 製剤例（凍結製剤） 注射用蒸留水１００ｍｌ中に、ｐＧｌｕ−Ａｓｎ−Ｓｅ
ｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の酢酸塩５ｍｇ、
およびＤ−マンニット５ｇを含有させ、ｐＨをリン酸緩
衝液で６．０〜８．０に調節した水溶液を調整した。こ
れを細菌濾過し、バイアル瓶に１ｍｌ分中した後、凍結
乾燥を行い、凍結乾燥注射剤を製造した。Example 2 Formulation example (frozen formulation) pGlu-Asn-Se in 100 ml of distilled water for injection
5 mg of r-Pro-Arg-Gly-NH 2 acetate,
And 5 g of D-mannitol, and the pH of the aqueous solution was adjusted to 6.0 to 8.0 with a phosphate buffer. This was subjected to bacterial filtration, and the resulting solution was placed in a vial for 1 ml, and then freeze-dried to produce a freeze-dried injection.
【００１５】実施例３ 抗不安作用 （方法）実験はｄｄＹ系マウスを用いて高架式十字型迷
路法で行った。この装置は各２本のオープン・アーム
（ｏｐｅｎ ａｒｍ）とエンクローズド・アーム（ｅｎ
ｃｌｏｓｅｄ ａｒｍ）からなり、これらのアームは中
央のプラットホーム部分から十文字に延びている。ま
た、この十字型迷路は床から５０ｃｍの高さに設置し
た。なお、オープン・アームおよびプラットホームは白
色に、エンクローズド・アームは黒色に塗装した。被験
薬物は試験開始１時間前に投与した。なお被験薬物のう
ちｐＧｌｕ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ
−ＮＨ2 の酢酸塩は生理食塩水に溶解し、ジアゼパムは
クレモホレール（ｃｒｅｍｏｐｈｏｒｅｌ）を生理食塩
水で１０％溶液としたものに懸濁させたものを用いた。Example 3 Anti-anxiety effect (Method) The experiment was carried out by an elevated cross maze method using ddY mice. This device consists of two open arms and two closed arms.
closed arms), these arms extending crosswise from the central platform portion. The cross-shaped maze was set at a height of 50 cm from the floor. The open arms and platforms were painted white, and the enclosed arms were painted black. The test drug was administered one hour before the start of the test. Among the test drugs, pGlu-Asn-Ser-Pro-Arg-Gly
Acetate -NH 2 was dissolved in saline, diazepam used was suspended in those with 10% solution Kuremohoreru the (Cremophor EL) with saline.
【００１６】（結果）本発明の有効成分であるｐＧｌｕ
−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の
酢酸塩は１μｇ／ｋｇ（皮下投与）においてマウスのオ
ープン・アームへの進入回数をコントロール群と比較し
て有意に増加した。また、オープン・アームでの滞在時
間は０．１μｇ／ｋｇ（皮下投与）においてコントロー
ル群と比較して有意に延長した。一方、公知の抗不安薬
であるジアゼパムは１ｍｇ／ｋｇ（皮下投与）において
マウスのオープン・アームへの進入回数をコントロール
群と比較して有意に増加した。また、オープン・アーム
での滞在時間は０．５ｍｇおよび１ｍｇ／ｋｇ（皮下投
与）においてコントロール群と比較して有意に延長し
た。従って、本発明の有効成分であるｐＧｌｕ−Ａｓｎ
−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の酢酸塩は
ジアゼパムと比較して１／１，０００〜１／５，０００
の用量で同様な効果を示すことが明らかになった。(Results) pGlu which is an active ingredient of the present invention
Acetate -Asn-Ser-Pro-Arg- Gly-NH 2 was significantly increased as compared to the control group number of entries into the open arms of the mouse at 1 [mu] g / kg (subcutaneous administration). In addition, the residence time in the open arm was significantly prolonged at 0.1 μg / kg (subcutaneous administration) as compared with the control group. On the other hand, diazepam, which is a known anxiolytic drug, significantly increased the number of mice entering the open arm at 1 mg / kg (subcutaneous administration) as compared with the control group. The stay time in the open arm was significantly prolonged at 0.5 mg and 1 mg / kg (subcutaneous administration) as compared with the control group. Therefore, the active ingredient of the present invention, pGlu-Asn
Acetate -Ser-Pro-Arg-Gly- NH 2 is compared to the diazepam 1 / 1,000 to / 5,000
It was found that a similar effect was obtained at the dose of.
【００１７】実施例４ 抗うつ作用 （方法）実験はｄｄＹ系マウスを用いて行った。直径１
８ｃ、高さ６０ｃｍの円筒形容器に水を１５ｃｍまで入
れ、プール内でのマウスの水泳行動を観察した。マウス
の両後肢が静止した状態を無動状態とみなし、１日１回
１５分間の測定を３日間行った。各群の平均無動時間が
均等になるよう群分けを行い、４日目同条件下で泳がせ
１５分間における無動時間を５分間ごとに測定した。被
験薬物は、Ｐｏｒｓｏｌｔ，Ｒ．Ｄ．らの方法（Ａｒｃ
ｈ．ｉｎｔ．Ｐｈａｒｍａｃｏｄｙｎ．，２２９，３２
７−３３６，１９７７；Ｎａｔｕｒｅ，２６６，７３０
−７３２，１９７７）に従って測定開始２４，５および
１時間前の計３回投与した。なお被験薬物であるｐＧｌ
ｕ−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2
の酢酸塩およびアミトリプチリン（ａｍｉｔｒｉｐｔｙ
ｌｉｎｅ ｈｙｄｒｏｃｈｌｏｒｉｄｅ）は生理食塩水
に溶解したものを用いた。Example 4 Antidepressant Action (Method) Experiments were performed using ddY mice. Diameter 1
8c, water was poured into a cylindrical container having a height of 60 cm up to 15 cm, and the swimming behavior of the mouse in the pool was observed. The state in which both hind limbs of the mouse were stationary was regarded as an immobile state, and measurement was performed once a day for 15 minutes for 3 days. The groups were divided so that the average immobility time of each group was equal, and the subjects were allowed to swim under the same conditions on day 4, and the immobility time during 15 minutes was measured every 5 minutes. The test drug was Porsolt, R.A. D. Method (Arc
h. int. Pharmacodyn. , 229,32
7-336, 1977; Nature, 266, 730
732, 1977), a total of 3 doses were given 24, 5 and 1 hour before the start of measurement. The test drug pGl
u-Asn-Ser-Pro-Arg-Gly-NH 2
Acetate and amitriptyline
Line hydrochloride used was dissolved in physiological saline.
【００１８】（結果）本発明の有効成分であるｐＧｌｕ
−Ａｓｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の
酢酸塩は０．１及び１μｇ／ｋｇ（皮下投与）において
測定時間のいずれの５分間の無動時間もコントロール群
に比較して有意に短縮した。また、０．０１μｇ／ｋｇ
（皮下投与）においても測定開始５分以降の無動時間を
有意に短縮した。一方、公知の抗うつ薬であるアミトリ
プチリンは５および１５ｍｇ／ｋｇ（皮下投与）におい
て測定開始５分間の無動時間をコントロール群と比較し
て有意に短縮したが、その結果は５ｍｇ／ｋｇのほうが
強力であった。なお、測定５〜１０分さらに１０〜１５
分で効果が減弱し有意差が認められなくなった。以上の
結果から、本発明の有効成分であるｐＧｌｕ−Ａｓｎ−
Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の酢酸塩はア
ミトリプチリンと比較して１／５００，０００の用量で
同様の効果をより持続性をもって示した。(Results) pGlu which is an active ingredient of the present invention
Acetate -Asn-Ser-Pro-Arg- Gly-NH 2 was significantly reduced compared to the immobility time is also a control group of either 5 minutes measurement time in 0.1 and 1 [mu] g / kg (subcutaneous administration) did. In addition, 0.01 μg / kg
(Subcutaneous administration) also significantly reduced the immobility time 5 minutes after the start of measurement. On the other hand, amitriptyline, a known antidepressant, significantly reduced the immobility time at the start of measurement at 5 and 15 mg / kg (subcutaneous administration) for 5 minutes as compared with the control group, but the result was 5 mg / kg. It was powerful. In addition, 5-10 minutes of measurement, and 10-15 minutes
The effect diminished in minutes and no significant difference was observed. From the above results, pGlu-Asn- which is an active ingredient of the present invention.
Acetate Ser-Pro-Arg-Gly- NH 2 exhibited with more persistent the same effect at a dose of 1 / 500,000 compared with amitriptyline.
【００１９】実施例５ 毒性 ＳＤ系ラットに本発明の有効成分であるｐＧｌｕ−Ａｓ
ｎ−Ｓｅｒ−Ｐｒｏ−Ａｒｇ−Ｇｌｙ−ＮＨ2 の酢酸塩
を１ｍｇ／ｋｇ皮下投与したが特記すべき変化は観察さ
れなかった。Example 5 Toxicity pGlu-As, an active ingredient of the present invention, was used in SD rats.
When 1 mg / kg of n-Ser-Pro-Arg-Gly-NH 2 acetate was subcutaneously administered, no remarkable change was observed.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 平手 謙二 埼玉県三郷市彦川戸１−22 日本ケミファ 株式会社研究所内 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Kenji Hirate 1-22 Hikogawado Misato-shi, Saitama
Claims (4)
又はＯＨを表す） で表されるペプチド又はそれらの薬理学的に許容される
塩を有効成分として含有する抗不安薬。1. The following general formula (I): A-Asn-Ser-Pro-Arg-Gly-B (I) wherein A represents pGlu or H, and B represents NH 2
Or an OH) or a pharmacologically acceptable salt thereof as an active ingredient.
有効成分として含有する抗不安薬。2. An anti-drug comprising a peptide represented by the following formula (II): pGlu-Asn-Ser-Pro-Arg-Gly-NH 2 (II) or a pharmacologically acceptable salt thereof as an active ingredient. Anxiety medication.
又はＯＨを表す） で表されるペプチド又はそれらの薬理学的に許容される
塩を有効成分として含有する抗うつ薬。3. The following general formula (I): A-Asn-Ser-Pro-Arg-Gly-B (I) wherein A represents pGlu or H, and B represents NH 2
Or OH) or a pharmacologically acceptable salt thereof as an active ingredient.
有効成分として含有する抗うつ薬。4. An anti-drug containing a peptide represented by the following formula (II): pGlu-Asn-Ser-Pro-Arg-Gly-NH 2 (II) or a pharmacologically acceptable salt thereof as an active ingredient. Depressive medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9362814A JPH11171786A (en) | 1997-12-12 | 1997-12-12 | Psychotropic agent containing peptide as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9362814A JPH11171786A (en) | 1997-12-12 | 1997-12-12 | Psychotropic agent containing peptide as active ingredient |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11171786A true JPH11171786A (en) | 1999-06-29 |
Family
ID=18477799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9362814A Pending JPH11171786A (en) | 1997-12-12 | 1997-12-12 | Psychotropic agent containing peptide as active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11171786A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001017545A1 (en) * | 1999-09-09 | 2001-03-15 | Nippon Chemiphar Co., Ltd. | Remedies for nervous diseases |
| JP2014162735A (en) * | 2013-02-22 | 2014-09-08 | Kyoto Univ | Antidepressant agent or anti-anxiety agent |
-
1997
- 1997-12-12 JP JP9362814A patent/JPH11171786A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001017545A1 (en) * | 1999-09-09 | 2001-03-15 | Nippon Chemiphar Co., Ltd. | Remedies for nervous diseases |
| JP2014162735A (en) * | 2013-02-22 | 2014-09-08 | Kyoto Univ | Antidepressant agent or anti-anxiety agent |
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