JPS6230168B2 - - Google Patents
Info
- Publication number
- JPS6230168B2 JPS6230168B2 JP2110779A JP2110779A JPS6230168B2 JP S6230168 B2 JPS6230168 B2 JP S6230168B2 JP 2110779 A JP2110779 A JP 2110779A JP 2110779 A JP2110779 A JP 2110779A JP S6230168 B2 JPS6230168 B2 JP S6230168B2
- Authority
- JP
- Japan
- Prior art keywords
- indenyloxymethyl
- morpholine
- methanol
- amitriptyline
- acid addition
- 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.)
- Expired
Links
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- MADRVGBADLFHMO-GFCCVEGCSA-N (2r)-2-(3h-inden-4-yloxymethyl)morpholine Chemical compound C=1C=CC=2C=CCC=2C=1OC[C@H]1CNCCO1 MADRVGBADLFHMO-GFCCVEGCSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 230000002996 emotional effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 16
- 239000000935 antidepressant agent Substances 0.000 description 7
- 229940005513 antidepressants Drugs 0.000 description 7
- 229960000836 amitriptyline Drugs 0.000 description 6
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- KEBHLNDPKPIPLI-UTONKHPSSA-N (2r)-2-(3h-inden-4-yloxymethyl)morpholine;hydrochloride Chemical compound Cl.C=1C=CC=2C=CCC=2C=1OC[C@H]1CNCCO1 KEBHLNDPKPIPLI-UTONKHPSSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- MADRVGBADLFHMO-UHFFFAOYSA-N Indeloxazine Chemical compound C=1C=CC=2C=CCC=2C=1OCC1CNCCO1 MADRVGBADLFHMO-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229960003914 desipramine Drugs 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- -1 lithium dibenzoyltartrate Chemical compound 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000003568 synaptosome Anatomy 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- YONLFQNRGZXBBF-KBPBESRZSA-N (2s,3s)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@H](C(=O)O)[C@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-KBPBESRZSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000008717 functional decline Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- KEBHLNDPKPIPLI-UHFFFAOYSA-N hydron;2-(3h-inden-4-yloxymethyl)morpholine;chloride Chemical compound Cl.C=1C=CC=2C=CCC=2C=1OCC1CNCCO1 KEBHLNDPKPIPLI-UHFFFAOYSA-N 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- ZEABYRLMGDTEAI-UHFFFAOYSA-M lithium;methanol;hydroxide Chemical compound [Li+].[OH-].OC ZEABYRLMGDTEAI-UHFFFAOYSA-M 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229960001158 nortriptyline Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 231100000691 up-and-down procedure Toxicity 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 本発明は、式[Detailed description of the invention] The present invention is based on the formula
【式】で示される
ｄ−２−（７−インデニルオキシメチル）モルホ
リンのｄ体またはその酸付加塩を有効成分とする
抗うつ剤に関する。酸付加塩としては、塩酸塩、
硫酸塩、マレイン酸塩などが好適である。
従来、うつ病の発症は脳内の神経伝達物質であ
るセロトニン（５−ヒドロキシトリプタミン、５
−HTと略記する）およびノルエピネフリン（NE
と略記する）の機能低下が重要視されており、５
−HTおよびNEの機能低下は、夫々うつ病患者の
「気分の低下」および「行動の低下」に関係する
と言われている。従来汎用されている抗うつ剤の
うち、イミプラミンおよびアミトリプチリンは５
−HTとNEの双方の機能を亢進させるのに対し、
デシプラミンおよびノルトリプチリンはNEの機
能を亢進させる薬剤であると言われている。
最近これらの薬剤と異なり５−HTの機能を選
択的に亢進させる新しいタイプの抗うつ剤の研究
開発が行なわれており、一部臨床的に有効なもの
も報告されている。この薬剤は、広義の抗うつ剤
とは治療上区別され、感情賦活剤と称される新し
いタイプに属する感情調整剤である。
ところで、２−（７−インデニルオキシメチ
ル）モルホリンおよびその酸付加塩は、本出願人
会社の研究者等によつて始めて製造された化合物
（アメリカ特許No.4109088）であり、その薬理作
用は、ラセミ体（dl体）に関し、５−HTおよび
NE双方の機能を亢進する有用な抗うつ剤である
ことが報告されている〔Neurochemical
Research、(3)657（1978）〕。本発明者等は光学的
活性体であるｄ体およびｌ体の薬理作用を検討し
た結果、意外にもｄ体がラセミ体（dl体）および
ｌ体と異なりNEの機能を殆んど亢進させず、５
−HTの機能を選択的に亢進させることを見出
し、本発明を完成したものである。
ｄ−２−（７−インデニルオキシメチル）モル
ホリン塩酸塩の有する各種薬理作用を、ｌ体およ
びラセミ体と対比して示すとつぎの通りである。
(1) ラツト脳シナプトゾーム（synaptosome）に
よるC14−５−HTおよびC14−NEの取込に対す
る阻害作用
阻害作用
実験方法および結果；
雄性ウイスターラツト（体重250−320ｇ）を
断首し、全脳あるいは海馬を採取した。de
Robertisらの方法〔Ｊ、Neurochem、９、23−
35（1962）〕に従つて粗ミトコンドリア分画を
調整し、Schachtらの方法〔Biochem、
Pharmacol、23、3413−3422（1974）〕に準じ
て脳シナプトゾームによるC14−５−HT（全
脳）およびC14−NE（海馬）の取込を測定し
た。試料の各濃度における取込阻害作用の強さ
から用量−作用曲線を描き、50％抑制濃度
（IC50：μＭ）を求めた。各用量ごとに少なく
とも６標本を用いた。結果を表に示す。The present invention relates to an antidepressant containing the d-form of d-2-(7-indenyloxymethyl)morpholine represented by the formula or an acid addition salt thereof as an active ingredient. Acid addition salts include hydrochloride,
Sulfates, maleates, etc. are suitable. Traditionally, the onset of depression has been linked to the neurotransmitter serotonin (5-hydroxytryptamine, 5-hydroxytryptamine) in the brain.
-HT) and norepinephrine (NE
5).
- It is said that the functional decline of HT and NE is related to "decreased mood" and "decreased behavior," respectively, in patients with depression. Among the conventionally widely used antidepressants, imipramine and amitriptyline are 5
−While it enhances the functions of both HT and NE,
Desipramine and nortriptyline are said to be drugs that enhance the function of NE. Recently, research and development has been carried out on new types of antidepressants that selectively enhance the function of 5-HT, unlike these drugs, and some of them have been reported to be clinically effective. This drug is therapeutically distinct from antidepressants in a broad sense, and is a new type of emotion regulator called an emotion activator. By the way, 2-(7-indenyloxymethyl)morpholine and its acid addition salts are compounds (US Patent No. 4109088) that were first manufactured by researchers at the applicant company, and their pharmacological actions are , regarding racemic body (dl body), 5-HT and
It has been reported that it is a useful antidepressant that enhances both NE functions [Neurochemical
Research, (3)657 (1978)]. The present inventors investigated the pharmacological effects of optically active forms, d-form and l-form, and found that, surprisingly, unlike racemic form (dl-form) and l-form, d-form almost enhances the function of NE. zu, 5
-The present invention was completed by discovering that the function of HT can be selectively enhanced. The various pharmacological actions of d-2-(7-indenyloxymethyl)morpholine hydrochloride are shown below in comparison with the l-form and racemic form. (1) Inhibitory effect on uptake of C14-5 -HT and C14 -NE by rat brain synaptosome Experimental method and results: Male Wistar rats (weight 250-320 g) were decapitated, and the whole brain Alternatively, the hippocampus was harvested. de
The method of Robertis et al. [J, Neurochem, 9 , 23-
35 (1962)] and the method of Schacht et al. [Biochem,
Pharmacol, 23 , 3413-3422 (1974)], the uptake of C14-5 -HT (whole brain) and C14 -NE (hippocampus) by brain synaptosomes was measured. A dose-effect curve was drawn based on the strength of the uptake inhibitory effect at each concentration of the sample, and the 50% inhibitory concentration (IC50: μM) was determined. At least 6 specimens were used for each dose. The results are shown in the table.
【表】
表１に示されるように、ｄ−体は５−HT取込
阻害作用においてdl−体、ｌ−体およびアミト
リプチリンとほぼ同じであるが、NE取込阻害
作用ではdl−体、ｌ−体およびアミトリプチリ
ンより著しく弱い。両作用の効力比（Ｂ／Ａ）
は、dl−体を1.0とすると、ｌ−体およびアミ
トリプチリンがほぼ同じであるのに対し、ｄ−
体は実に22倍であり、５−HTに対する高い選
択性が認められる。一方、NEの機能を亢進す
る薬剤であると言われているデシプラミンは
NEに対し、高い選択性を有している。
(2) 急性毒性
雄性ICRマウス（体重25−32ｇ）にｄ−２−
（７−インデニルオキシメチル）モルホリン塩
酸塩を静脈内投与し、up and down法により
LD50（mg／Kg）を求めた。
LD50（i.v.）49mg／Kg
なお、投与後72時間まで観察したが、投与後
30分以降に死亡する例はなかつた。
以上の実験結果から明らかなように、ｄ−２−
（７−インデニルオキシメチル）モルホリンまた
はその酸付加塩は、dl−２−（７−インデニルオ
キシメチル）モルホリンまたはその酸付加塩およ
びそのｌ−体と異なり選択的セロトニン（５−
HT）機能亢進作用を有するので、うつ病の中で
もセロトニンの機能低下が主な原因と考えられる
患者の治療、症状の改善のための医薬として有用
である。
本発明の抗うつ剤は、そのままあるいは適宜の
薬理的に許容される担体、賦形剤、希釈剤と混合
し、散剤、顆粒剤、錠剤、カプセル剤、注射剤、
坐剤などの形態で経口的または非経口的に投与す
ることができる。たとえば、成人の場合、以下の
処方を有する錠剤を１日２錠から12錠を経口的に
投薬されるが、年令、体重、症状などにより投与
量が増減されることはいうまでもない。
処方例
ｄ−２−（７−インデニルオキシメチル）モル
ホリン塩酸塩 25mg
乳 糖 70mg
デンプン 25mg
タルク ４mg
ステアリン酸マグネシウム １mg
上記成分を混合し、顆粒化した後、常法により
打錠して１錠125mgの錠剤を製造する。
なお、本発明の抗うつ剤の有効成分であるｄ−
２−（７−インデニルオキシメチル）モルホリン
の理化学的性状並びにラセミ体からの分離方法
を、つぎの参考例に示す。
参考例
ｄ−ジベンゾイル酒石酸のメタノール溶液に水
酸化リチウムメタノール溶液を加えて調製したｄ
−ジベンゾイル酒石酸リチウムのメタノール溶液
に、等モルのdl−２−（７−インデニルオキシメ
チル）モルホリン塩酸塩のメタノール溶液を加
え、室温で２昼夜かきまぜる。析出した結晶を
取し、メタノールで５回次いでエタノールで５回
再結晶して、ｄ−２−（７−インデニルオキシメ
チル）モルホリン・ｄ−ジベンゾイル酒石酸塩
（１：1/2）を得た。〔α〕２０ Ｄ−51（Ｃ＝0.7、メタ
ノール）この塩をメタノールに溶かした溶液をあ
らかじめクロルイオンで置換したアンバーリース
トA21（イオン交換樹脂）に通し、メタノールを
留去後、残留物をエタノールで再結晶してｄ−２
−（７−インデニルオキシメチル）モルホリン塩
酸塩を得た。融点147−148℃、〔α〕２０ ４３６＋12.4
（Ｃ
＝3.05、メタノール）
また、母液よりメタノールを留去した後、エー
テルを加え、析出した結晶を取し、10％含水メ
タノールで９回再結晶してｌ−２−（７−インデ
ニルオキシメチル）モルホリン・ｄ−ジベンゾイ
ル酒石酸塩（１：1/2）を得た。〔α〕２０ Ｄ−53（Ｃ
＝0.7、メタノール）この塩を上記と同様に処理
してｌ−２−（７−インデニルオキシメチル）モ
ルホリン塩酸塩を得た。融点143〜146℃、〔α〕
２０ ４３６−11.8（Ｃ＝3.14、メタノール）[Table] As shown in Table 1, the d-form is almost the same as the dl-form, l-form and amitriptyline in its 5-HT uptake inhibitory action, but the d-form, l-form and amitriptyline in its NE uptake inhibitory action. - Significantly weaker than amitriptyline and amitriptyline. Efficacy ratio of both effects (B/A)
If the dl-form is 1.0, the l-form and amitriptyline are almost the same, whereas the d-form is almost the same.
The body is actually 22 times more selective, indicating high selectivity for 5-HT. On the other hand, desipramine, which is said to be a drug that enhances NE function,
It has high selectivity for NE. (2) Acute toxicity D-2-
(7-indenyloxymethyl)morpholine hydrochloride was administered intravenously and by the up and down method.
LD 50 (mg/Kg) was determined. LD 50 (iv) 49mg/Kg Although observations were made for up to 72 hours after administration,
There were no cases of death after 30 minutes. As is clear from the above experimental results, d-2-
(7-indenyloxymethyl)morpholine or its acid addition salt differs from dl-2-(7-indenyloxymethyl)morpholine or its acid addition salt and its l-form in selective serotonin (5-
HT), it is useful as a drug for treating patients whose main cause of depression is thought to be decreased serotonin function, and for improving symptoms. The antidepressant of the present invention can be used as it is or mixed with appropriate pharmacologically acceptable carriers, excipients, and diluents to form powders, granules, tablets, capsules, injections, etc.
It can be administered orally or parenterally in the form of suppositories and the like. For example, in the case of adults, 2 to 12 tablets per day with the following prescription are administered orally, but it goes without saying that the dosage may be increased or decreased depending on age, body weight, symptoms, etc. Prescription example d-2-(7-indenyloxymethyl)morpholine hydrochloride 25mg Lactose 70mg Starch 25mg Talc 4mg Magnesium stearate 1mg The above ingredients are mixed, granulated, and then tableted in a conventional manner to give 1 tablet 125mg. manufactures tablets. In addition, d- which is the active ingredient of the antidepressant of the present invention
The physical and chemical properties of 2-(7-indenyloxymethyl)morpholine and the method for separating it from the racemate are shown in the following reference example. Reference example d prepared by adding lithium hydroxide methanol solution to a methanol solution of d-dibenzoyltartaric acid
- Add an equimolar methanol solution of dl-2-(7-indenyloxymethyl)morpholine hydrochloride to a methanol solution of lithium dibenzoyltartrate, and stir at room temperature for two days and nights. The precipitated crystals were collected and recrystallized five times with methanol and then five times with ethanol to obtain d-2-(7-indenyloxymethyl)morpholine/d-dibenzoyltartrate (1:1/2). . [α] 20 D -51 (C = 0.7, methanol) A solution of this salt in methanol was passed through Amberlyst A21 (ion exchange resin) which had been replaced with chlorine ions in advance, and after distilling off the methanol, the residue was dissolved in ethanol. Recrystallize with d-2
-(7-indenyloxymethyl)morpholine hydrochloride was obtained. Melting point 147-148℃, [α] 20 436 +12.4
(C
= 3.05, methanol) Also, after distilling off methanol from the mother liquor, ether was added, the precipitated crystals were collected, and recrystallized nine times with 10% aqueous methanol to obtain l-2-(7-indenyloxymethyl). Morpholine d-dibenzoyltartrate (1:1/2) was obtained. [α] 20 D −53 (C
=0.7, methanol) This salt was treated in the same manner as above to obtain 1-2-(7-indenyloxymethyl)morpholine hydrochloride. Melting point 143-146℃, [α]
20 436 -11.8 (C=3.14, methanol)
Claims (1)
ルホリンまたはその酸付加塩を有効成分とする感
情賦活剤。1 An emotional stimulant containing d-2-(7-indenyloxymethyl)morpholine or an acid addition salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2110779A JPS55113717A (en) | 1979-02-24 | 1979-02-24 | Antidepressive drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2110779A JPS55113717A (en) | 1979-02-24 | 1979-02-24 | Antidepressive drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55113717A JPS55113717A (en) | 1980-09-02 |
| JPS6230168B2 true JPS6230168B2 (en) | 1987-07-01 |
Family
ID=12045645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2110779A Granted JPS55113717A (en) | 1979-02-24 | 1979-02-24 | Antidepressive drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55113717A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521180A (en) * | 1993-02-10 | 1996-05-28 | Yamanouchi Pharmaceutical Co., Ltd. | Morpholine derivative |
-
1979
- 1979-02-24 JP JP2110779A patent/JPS55113717A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55113717A (en) | 1980-09-02 |
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