JP2002154962A - Antidepressant/antianxiety agent comprising isoquinoline derivative - Google Patents
Antidepressant/antianxiety agent comprising isoquinoline derivativeInfo
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- JP2002154962A JP2002154962A JP2001345860A JP2001345860A JP2002154962A JP 2002154962 A JP2002154962 A JP 2002154962A JP 2001345860 A JP2001345860 A JP 2001345860A JP 2001345860 A JP2001345860 A JP 2001345860A JP 2002154962 A JP2002154962 A JP 2002154962A
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- antidepressant
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Abstract
Description
【0001】[0001]
【産業上の利用分野】本発明は、イソキノリン誘導体及
びその薬学的に許容される塩の少なくとも一種を有効成
分として含有する抗鬱、抗不安剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antidepressant or anxiolytic comprising at least one of an isoquinoline derivative and a pharmaceutically acceptable salt thereof as an active ingredient.
【0002】[0002]
【従来の技術】細胞内情報伝達物質としてのcAMPや
cGMPの細胞機能調節作用が明らかにされ、その分解
酵素である環状ヌクレオチドホスホジエステラーゼに関
しても研究が行われている。環状ヌクレオチドホスホジ
エステラーゼは単にホスホジエステラーゼと略称される
ことが多く、いくつかのアイソザイムに分類され、各ア
イソザイムの分子構造、調節機構、組織・細胞内分布、
特異性が明らかされつつある。それに伴って、ホスホジ
エステラーゼのアイソザイムに特異的な阻害剤の研究も
盛んであり、医薬等として有用な阻害剤が見出されてい
る。2. Description of the Related Art The function of cAMP and cGMP as intracellular signaling substances to regulate cell functions has been elucidated, and studies have been conducted on cyclic nucleotide phosphodiesterase, which is a degrading enzyme thereof. Cyclic nucleotide phosphodiesterases are often abbreviated simply as phosphodiesterases, are classified into several isozymes, and have the molecular structure, regulatory mechanism, tissue / cellular distribution,
Specificity is being revealed. Along with this, studies on inhibitors specific to phosphodiesterase isozymes have been actively conducted, and useful inhibitors as pharmaceuticals and the like have been found.
【0003】ホスホジエステラーゼのアイソザイムの一
つであるホスホジエステラーゼIV型アイソザイム(以
下、PDEIVと略称する)は、脳、腎臓、精巣、炎症細
胞等の組織や細胞に分布しており、cAMPに対するK
m値が低く、cAMPの特異的分解酵素である。このP
DEIVを阻害することにより組織内cAMP濃度が上昇
するため、PDEIVの阻害物質は種々の薬理作用、例え
ば抗鬱作用、抗不安作用、抗痴呆作用等の中枢に対する
作用、ケミカルメディエーター遊離抑制や好中球の浸潤
抑制による抗炎症作用、気管支拡張作用、平滑筋弛緩作
用、肝保護作用、利尿作用などを有することが知られて
いる。[0003] Phosphodiesterase type IV isozyme (hereinafter abbreviated as PDEIV), which is one of the phosphodiesterase isozymes, is distributed in tissues and cells such as brain, kidney, testis, and inflammatory cells.
It has a low m value and is a specific cAMP-degrading enzyme. This P
Since inhibition of DEIV increases cAMP concentration in tissues, PDEIV inhibitors have various pharmacological effects such as antidepressant, anti-anxiety, anti-dementia effects on central nervous system, chemical mediator release inhibition and neutrophils. It is known to have an anti-inflammatory action, a bronchodilator action, a smooth muscle relaxation action, a hepatoprotective action, a diuretic action, etc., by suppressing the infiltration of spheres.
【0004】イソキノリン誘導体に関しては、末梢血管
拡張作用や鎮痙作用等の薬理作用を有するものが知られ
ており、ドロタベリン等は実際に医薬として用いられて
いる。本発明者らはイソキノリン誘導体の新しい薬理作
用に関して鋭意研究した結果、本発明イソキノリン誘導
体がPDEIVに対して特異性の高い優れた阻害活性を有
することを見出し、本発明を完成した。As the isoquinoline derivatives, those having pharmacological actions such as peripheral vasodilatory action and antispasmodic action are known, and drotaverine and the like are actually used as medicines. The present inventors have conducted intensive studies on new pharmacological actions of isoquinoline derivatives, and as a result, have found that the isoquinoline derivatives of the present invention have an excellent inhibitory activity with high specificity for PDEIV, and completed the present invention.
【0005】[0005]
【発明が解決しようとする課題】本発明の目的は、優れ
たPDEIV阻害作用を有するイソキノリン誘導体を有効
成分として含有する新規な抗鬱、抗不安剤を提供するこ
とにある。SUMMARY OF THE INVENTION An object of the present invention is to provide a novel antidepressant or anxiolytic containing an isoquinoline derivative having an excellent PDEIV inhibitory activity as an active ingredient.
【0006】[0006]
【課題を解決するための手段】本発明抗鬱、抗不安剤の
活性成分は、下記一般式で示されるイソキノリン誘導体
である。The active ingredient of the antidepressant and anxiolytic agent of the present invention is an isoquinoline derivative represented by the following general formula.
【化2】 〔式中、Rはエトキシ基を表す。〕Embedded image [In the formula, R represents an ethoxy group. ]
【0007】本発明イソキノリン誘導体は、前記一般式
で表される化合物の薬学的に許容される塩を包含し、例
えば、塩酸、硫酸、硝酸、臭化水素酸、リン酸、過塩素
酸、チオシアン酸、ホウ酸、ギ酸、酢酸、ハロ酢酸、プ
ロピオン酸、グリコール酸、クエン酸、酒石酸、コハク
酸、グルコン酸、乳酸、マロン酸、フマール酸、アント
ラニル酸、安息香酸、ケイ皮酸、p−トルエンスルホン
酸、ナフタレンスルホン酸、スルファニル酸、テオフィ
リン−酢酸等との酸付加塩を挙げることができ、好まし
くは塩酸、テオフィリン−酢酸等との塩であり、これら
の塩は公知の方法により、遊離の本発明イソキノリン誘
導体より製造でき或いは相互に変換できる。The isoquinoline derivative of the present invention includes a pharmaceutically acceptable salt of the compound represented by the above general formula, for example, hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid, phosphoric acid, perchloric acid, thiocyanate Acid, boric acid, formic acid, acetic acid, haloacetic acid, propionic acid, glycolic acid, citric acid, tartaric acid, succinic acid, gluconic acid, lactic acid, malonic acid, fumaric acid, anthranilic acid, benzoic acid, cinnamic acid, p-toluene Sulfonic acid, naphthalenesulfonic acid, sulfanilic acid, acid addition salts with theophylline-acetic acid and the like can be mentioned, preferably hydrochloric acid, salts with theophylline-acetic acid and the like, and these salts are free by known methods. It can be produced from the isoquinoline derivative of the present invention or can be mutually converted.
【0008】また本発明化合物においてシス−トランス
異性体、光学異性体、配座異性体等の立体異性体が存在
する場合、或いは水和物の状態で存在する場合において
も、本発明はそのいずれの立体異性体及び水和物をも包
含する。[0008] Further, the present invention is not limited to the case where the compound of the present invention has stereoisomers such as cis-trans isomers, optical isomers and conformers, or exists in the form of hydrates. And hydrates thereof.
【0009】本発明化合物中特に好ましい化合物を例示
すれば以下のとおりである。 1−(3’,4’−ジエトキシベンジル)−6,7−ジ
エトキシ−3,4−ジヒドロイソキノリン〔化合物1〕 1−(3’,4’−ジエトキシベンジル)−6,7−ジ
エトキシ−3,4−ジヒドロイソキノリン塩酸塩〔化合
物2〕 1−(3’,4’−ジエトキシベンジル)−6,7−ジ
エトキシ−3,4−ジヒドロイソキノリン−テオフィリ
ン−7−アセテート〔化合物3〕 1−(3’,4’−ジエトキシベンジル)−6,7−ジ
エトキシ−3,4−ジヒドロイソキノリン−テオフィリ
ン−7−アセテート・1水和物〔化合物4〕[0009] Among the compounds of the present invention, particularly preferred compounds are as follows. 1- (3 ′, 4′-diethoxybenzyl) -6,7-diethoxy-3,4-dihydroisoquinoline [Compound 1] 1- (3 ′, 4′-diethoxybenzyl) -6,7-diethoxy- 3,4-dihydroisoquinoline hydrochloride [Compound 2] 1- (3 ', 4'-diethoxybenzyl) -6,7-diethoxy-3,4-dihydroisoquinoline-theophylline-7-acetate [Compound 3] 1- (3 ′, 4′-Diethoxybenzyl) -6,7-diethoxy-3,4-dihydroisoquinoline-theophylline-7-acetate monohydrate [Compound 4]
【0010】上記本発明化合物は、例えば特開昭50−
46818号公報、特開昭62−167781号公報、
特開昭62−187411号公報等に記載されており、
既知の方法で製造することができる。以下に本発明イソ
キノリン誘導体の薬理作用について述べる。The compound of the present invention is described in, for example,
No. 46818, Japanese Patent Application Laid-Open No. 62-167781,
It is described in JP-A-62-187411 and the like,
It can be manufactured by known methods. Hereinafter, the pharmacological action of the isoquinoline derivative of the present invention will be described.
【0011】[0011]
【作用】1.ホスホジエステラーゼ・アイソザイムの調
製 ホスホジエステラーゼの各アイソザイムを常法に従って
調製した。即ち、ブタ大動脈の凍結乾燥粉末10gに5
倍量(v/w)の緩衝液(0.25Mショ糖、10mM
トリス塩酸、pH7.8、5mM塩化マグネシウム、
0.2mMエチレンビス(オキシエチレンニトリロ)テ
トラ酢酸、100nMα−トルエンスルホニルフルオラ
イド、100nMロイペプチン、100nMペプスタチ
ン)を加えホモゲナイズした。これを2500rpmで
20分間遠心分離し、上清をさらに40000rpmで
1時間遠心分離した。得られた上清を濾過した後、上記
緩衝液と同様のプロテアーゼ阻害剤を含む溶液(70m
M酢酸ナトリウム、pH6.8、5mM2−メルカプト
エタノール)で透析した。[Action] Preparation of phosphodiesterase isozyme Each phosphodiesterase isozyme was prepared according to a conventional method. That is, 5 g to 10 g of lyophilized powder of porcine aorta.
Double volume (v / w) of buffer (0.25 M sucrose, 10 mM
Tris-HCl, pH 7.8, 5 mM magnesium chloride,
0.2 mM ethylene bis (oxyethylene nitrilo) tetraacetic acid, 100 nM α-toluenesulfonyl fluoride, 100 nM leupeptin, 100 nM pepstatin) were added and homogenized. This was centrifuged at 2500 rpm for 20 minutes, and the supernatant was further centrifuged at 40,000 rpm for 1 hour. After filtering the resulting supernatant, a solution containing the same protease inhibitor as the above buffer solution (70 m
M sodium acetate, pH 6.8, 5 mM 2-mercaptoethanol).
【0012】上記透析液で平衡化しカラムに充填したD
EAE−Sepharose−FFカラム(ファルマシ
ア社製)に、透析して得られた試料を添加し、酢酸ナト
リウムの0.07乃至1.0Mの直線的濃度勾配溶液で
溶出した。溶出フラクションについてホスホジエステラ
ーゼの各アイソザイムの活性測定を行い、活性の集中し
たフラクションを集めて酵素源として使用した。本試験
系においては、I型は20及び21番フラクションに、
II型は30及び31番フラクションに、 III型は29番
フラクションに、IV型は61番フラクションに、V型は
67番フラクションに各アイソザイムが溶出分画され
た。D was equilibrated with the above dialysate and packed in a column.
The sample obtained by dialysis was added to an EAE-Sepharose-FF column (manufactured by Pharmacia), and eluted with a linear concentration gradient solution of sodium acetate from 0.07 to 1.0M. The activity of each isozyme of phosphodiesterase was measured for the eluted fraction, and fractions with concentrated activities were collected and used as an enzyme source. In this test system, type I was in fractions 20 and 21,
The isozymes were eluted and fractionated in fractions 30 and 31 for type II, fraction 29 for type III, fraction 61 for type IV and fraction 67 for type V.
【0013】2.ホスホジエステラーゼ活性測定法 50mMトリス塩酸(pH7.5)、6mM塩化マグネ
シウム、1mMエチレンビス(オキシエチレンニトリ
ロ)テトラ酢酸、2.5mMジチオスレイトール、2.
5%ジメチルスルホキシド、0.025mg/ml5’
−ヌクレオチド、0.23mg/mlウシ血清アルブミ
ン及び1乃至5μgの各酵素を合わせて反応系を作成し
た(各値は最終濃度を示す)。この反応混合溶液を30
℃で5乃至10分間プレインキュベートした後、
〔 3H〕cAMP又は〔 3H〕cGMPを添加し、30
℃で10乃至15分間インキュベートした。水に懸濁し
た陽イオン交換樹脂を反応溶液に加え未反応cAMP又
はcGMPを吸着させ反応を停止させた後、2000g
で5分間遠心分離し、上清の一部を分取して液体シンチ
レーション・カウンターにて放射活性を測定した。ジメ
チルスルホキシド又は水に溶解した被検物質を上記反応
系に加え、該物質のホスホジエステラーゼの各アイソザ
イムに対する阻害活性を測定した。2. Method for measuring phosphodiesterase activity 50 mM Tris-HCl (pH 7.5), 6 mM magnesium chloride, 1 mM ethylenebis (oxyethylenenitriro) tetraacetic acid, 2.5 mM dithiothreitol, 2.
5% dimethyl sulfoxide, 0.025 mg / ml 5 '
-A reaction system was prepared by combining nucleotides, 0.23 mg / ml bovine serum albumin and 1 to 5 µg of each enzyme (each value indicates the final concentration). This reaction mixture solution is
After pre-incubation at 5 ° C for 5-10 minutes,
[ 3 H] cAMP or [ 3 H] cGMP was added, and 30
Incubated at 10 ° C for 10-15 minutes. After adding the cation exchange resin suspended in water to the reaction solution and absorbing unreacted cAMP or cGMP to stop the reaction, 2000 g
For 5 minutes, a part of the supernatant was collected, and the radioactivity was measured with a liquid scintillation counter. A test substance dissolved in dimethyl sulfoxide or water was added to the above reaction system, and the inhibitory activity of the substance on phosphodiesterase isozymes was measured.
【0014】I型アイソザイムに対する被検物質の阻害
活性を測定する場合は、基質に〔 3H〕cAMPを用
い、5μg/mlのカルモジュリンを共存させた。II型
に対する阻害活性測定の場合は、基質に〔 3H〕cAM
Pを用い、10μMのcGMPを共存させた。III型の
場合は、基質に〔 3H〕cAMPを用い、100μMの
Ro20−1724(4−〔(3−ブトキシ−4−メト
キシフェニル)メチル〕−2−イミダゾリジノン:IV型
特異的阻害剤)を共存させ、IV型の場合は、基質に〔 3
H〕cAMPを用い、10μMのシロスタゾール(III型
特異的阻害剤)を共存させて各アイソザイムに対する被
検物質の阻害活性を測定した。またV型の測定の場合
は、〔 3H〕cGMPを基質として用いた。When measuring the inhibitory activity of a test substance on the type I isozyme, [ 3 H] cAMP was used as a substrate, and 5 μg / ml of calmodulin was allowed to coexist. In the case of measuring the inhibitory activity on type II, the substrate was [ 3 H] cAM
P was used in the presence of 10 μM cGMP. In the case of type III, using [ 3 H] cAMP as a substrate, 100 μM of Ro20-1724 (4-[(3-butoxy-4-methoxyphenyl) methyl] -2-imidazolidinone: type IV specific inhibitor ) Coexist, and in the case of type IV, [ 3
H] Using cAMP, the inhibitory activity of the test substance on each isozyme was measured in the presence of 10 μM cilostazol (a type III specific inhibitor). In the case of V-type measurement, [ 3 H] cGMP was used as a substrate.
【0015】[0015]
【効果】上記試験方法に従ってホスホジエステラーゼの
各アイソザイムに対する阻害活性を測定した結果、本発
明化合物は特にIV型アイソザイムに対して強い阻害作用
を示した。結果の一例を表1に示す。[Effects] As a result of measuring the inhibitory activity of phosphodiesterase on each isozyme according to the test method described above, the compound of the present invention showed a strong inhibitory activity particularly on the type IV isozyme. Table 1 shows an example of the results.
【0016】[0016]
【表1】 [Table 1]
【0017】表1に示した結果から明らかなように、本
発明化合物は非常に特異的なPDEIV阻害剤として知ら
れているRo20−1724と同等若くはそれ以上のP
DEIV阻害活性を示し、且つそのPDEIV阻害活性は他
の型のPDEアイソザイムに対する阻害活性よりも10
倍以上強い特異的なものであった。前述したとおり、P
DEIVを阻害することにより組織内cAMP濃度が上昇
するため、抗鬱作用、抗不安作用、抗痴呆作用等の中枢
に対する作用、ケミカルメディエーター遊離抑制や好中
球の浸潤抑制による抗炎症作用、気管支拡張作用、平滑
筋弛緩作用、肝保護作用、利尿作用などがPDEIV阻害
剤の薬理効果として示唆されている。従って、本発明物
質は、抗鬱剤、抗不安剤等の薬剤として、鬱病等の中枢
系疾患を予防・治療するための医薬として非常に有用性
が高い。また本発明物質は、PDEIV阻害作用に基づ
き、肝保護剤や利尿剤としても有用である。As is evident from the results shown in Table 1, the compounds of the present invention have a P value equal to or higher than that of Ro20-1724 which is known as a very specific PDEIV inhibitor.
Exhibits a DEIV inhibitory activity, and its PDEIV inhibitory activity is 10% lower than the inhibitory activity against other types of PDE isozymes.
It was specific more than twice as strong. As mentioned above, P
Inhibition of DEIV causes an increase in cAMP concentration in tissues, which is a central effect such as antidepressant action, anxiolytic action, anti-dementia action, anti-inflammatory action by suppressing chemical mediator release and neutrophil infiltration, and bronchodilation Action, smooth muscle relaxing action, hepatoprotective action, diuretic action and the like have been suggested as pharmacological effects of PDEIV inhibitors. Therefore, the substance of the present invention is extremely useful as a drug such as an antidepressant or an anxiolytic, as a medicament for preventing or treating central nervous system diseases such as depression. Further, the substance of the present invention is also useful as a hepatoprotective agent or diuretic based on PDEIV inhibitory action.
【0018】[0018]
【実施例】本発明物質は、適当な医薬用の担体若しくは
希釈剤と組み合わせて医薬とすることができ、通常の方
法によって各種製剤化可能で、経口又は非経口投与する
ための固体、半固体、液体又はエアロゾールの剤形に処
方することができる。処方にあたっては、本発明物質を
単独で用いるか、あるいは他の医薬活性成分と適宜組み
合わせて処方してもよい。EXAMPLES The substance of the present invention can be made into a medicine by combining it with a suitable pharmaceutical carrier or diluent, can be formulated into various formulations by a usual method, and can be solid or semi-solid for oral or parenteral administration. , Liquid or aerosol dosage forms. In the formulation, the substance of the present invention may be used alone or may be combined with other pharmaceutically active ingredients as appropriate.
【0019】経口投与製剤としては、そのままあるいは
適当な添加剤、例えば乳糖、白糖、ブドウ糖、マンニッ
ト、トウモロコシデンプン、バレイショデンプン等の慣
用の賦形剤と共に、結晶セルロース、セルロース誘導
体、アラビアゴム、トラガント液、アルギン酸ナトリウ
ム液、ゼラチン等の結合剤、トウモロコシデンプン、バ
レイショデンプン、カルボキシメチルセルロースカリウ
ム等の崩壊剤、タルク、ステアリン酸マグネシウム等の
滑沢剤、その他増量剤、湿潤化剤、緩衝剤、保存剤、香
料等を適宜組み合わせて錠剤、散剤、顆粒剤或いはカプ
セル剤とすることができる。またカカオ脂等の油脂性基
剤、乳剤性基剤又はマクロゴール等の水溶性基剤、親水
性基剤等と混和して坐剤としてもよい。As the preparation for oral administration, crystalline cellulose, cellulose derivatives, gum arabic, tragacanth, as it is or with appropriate additives such as lactose, sucrose, glucose, mannitol, corn starch, potato starch and the like, can be used. Solution, sodium alginate solution, binders such as gelatin, disintegrants such as corn starch, potato starch, potassium carboxymethylcellulose, lubricants such as talc, magnesium stearate, other bulking agents, wetting agents, buffers, preservatives , Fragrances and the like can be appropriately combined into tablets, powders, granules or capsules. Also, suppositories may be prepared by mixing with an oily base such as cocoa butter, an emulsion base, a water-soluble base such as macrogol, or a hydrophilic base.
【0020】注射剤としては、水性溶剤又は非水性溶
剤、例えば注射用蒸溜水、生理食塩水、リンゲル液、植
物油、合成脂肪酸グリセリド、高級脂肪酸エステル、プ
ロピレングリコール等の溶液若しくは懸濁液とすること
ができる。また患者の状態や疾患の種類に応じて、その
治療に最適な上記以外の剤形、例えば吸入剤、エアゾー
ル剤、軟膏、パップ剤、点眼剤等に適宜製剤化すること
が可能である。The injection may be an aqueous solvent or a non-aqueous solvent, for example, a solution or suspension of distilled water for injection, physiological saline, Ringer's solution, vegetable oil, synthetic fatty acid glyceride, higher fatty acid ester, propylene glycol or the like. it can. Depending on the condition of the patient and the type of disease, it can be appropriately formulated into a dosage form other than the above, such as an inhalant, an aerosol, an ointment, a poultice, or an eye drop, which is optimal for the treatment.
【0021】本発明物質の望ましい投与量は、投与対象
(患者の年齢、体重、症状など)、剤形、投与方法、投
与期間等によって変わるが、所望の効果を得るには、一
般の成人に対して通常1日に10乃至2000mgを1
回乃至数回に分けて経口投与することができる。また注
射剤等の非経口投与の場合、吸収等の影響により、前記
経口投与量の3乃至10分の1の用量レベルの投与量が
好ましい。The desired dose of the substance of the present invention varies depending on the subject of administration (age, weight, symptoms, etc. of the patient), dosage form, administration method, administration period, and the like. On the other hand, usually 10 to 2000 mg per day
It can be orally administered once or several times. In the case of parenteral administration of an injection or the like, a dose at a dose level of 3 to 1/10 of the oral dose is preferable due to the influence of absorption and the like.
【0022】以下に本発明物質を有効成分として含有す
る医薬組成物の処方例を示すが、本発明はこれによって
限定されるものではない。[0022] Formulation examples of a pharmaceutical composition containing the substance of the present invention as an active ingredient are shown below, but the present invention is not limited thereto.
【表2】 [Table 2]
【0023】[0023]
【表3】 [Table 3]
フロントページの続き (51)Int.Cl.7 識別記号 FI テーマコート゛(参考) A61P 25/22 A61P 25/22 25/24 25/24 29/00 29/00 43/00 111 43/00 111 // C07D 217/20 C07D 217/20 Fターム(参考) 4C034 AK03 AK15 4C086 AA01 AA02 BC30 MA01 MA04 NA14 ZA05 ZA12 ZA59 ZA75 ZA81 ZA94 ZB11 ZC20 Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat II (reference) A61P 25/22 A61P 25/22 25/24 25/24 29/00 29/00 43/00 111 43/00 111 // C07D 217/20 C07D 217/20 F term (reference) 4C034 AK03 AK15 4C086 AA01 AA02 BC30 MA01 MA04 NA14 ZA05 ZA12 ZA59 ZA75 ZA81 ZA94 ZB11 ZC20
Claims (4)
体及びその薬学的に許容される塩の少なくとも一種を有
効成分として含有する抗鬱、抗不安剤。 【化1】 〔式中、Rはエトキシ基を表す。〕1. An antidepressant or anxiolytic comprising as an active ingredient at least one of an isoquinoline derivative represented by the following general formula and a pharmaceutically acceptable salt thereof. Embedded image [In the formula, R represents an ethoxy group. ]
キシベンジル)−6,7−ジエトキシ−3,4−ジヒド
ロイソキノリン塩酸塩である請求項1に記載の抗鬱、抗
不安剤。2. The antidepressant and anxiolytic agent according to claim 1, wherein the active ingredient is 1- (3 ′, 4′-diethoxybenzyl) -6,7-diethoxy-3,4-dihydroisoquinoline hydrochloride. .
キシベンジル)−6,7−ジエトキシ−3,4−ジヒド
ロイソキノリン−テオフィリン−7−アセテートである
請求項1に記載の抗鬱、抗不安剤。3. The antidepressant according to claim 1, wherein the active ingredient is 1- (3 ′, 4′-diethoxybenzyl) -6,7-diethoxy-3,4-dihydroisoquinoline-theophylline-7-acetate. , Anxiolytics.
キシベンジル)−6,7−ジエトキシ−3,4−ジヒド
ロイソキノリン−テオフィリン−7−アセテート・1水
和物である請求項1に記載の抗鬱、抗不安剤。4. The method according to claim 1, wherein the active ingredient is 1- (3 ′, 4′-diethoxybenzyl) -6,7-diethoxy-3,4-dihydroisoquinoline-theophylline-7-acetate monohydrate. An antidepressant and an anxiolytic according to any one of the above.
Priority Applications (1)
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JP2001345860A JP3782001B2 (en) | 2001-11-12 | 2001-11-12 | Antidepressant and anxiolytic agents containing isoquinoline derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2001345860A JP3782001B2 (en) | 2001-11-12 | 2001-11-12 | Antidepressant and anxiolytic agents containing isoquinoline derivatives |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP35148193A Division JP3276762B2 (en) | 1993-12-28 | 1993-12-28 | Pharmaceutical composition containing isoquinoline derivative |
Publications (2)
Publication Number | Publication Date |
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JP2002154962A true JP2002154962A (en) | 2002-05-28 |
JP3782001B2 JP3782001B2 (en) | 2006-06-07 |
Family
ID=19159134
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JP2001345860A Expired - Fee Related JP3782001B2 (en) | 2001-11-12 | 2001-11-12 | Antidepressant and anxiolytic agents containing isoquinoline derivatives |
Country Status (1)
Country | Link |
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JP (1) | JP3782001B2 (en) |
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2001
- 2001-11-12 JP JP2001345860A patent/JP3782001B2/en not_active Expired - Fee Related
Also Published As
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JP3782001B2 (en) | 2006-06-07 |
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