JP2625457B2 - Agents for preventing or alleviating nausea or vomiting - Google Patents

Agents for preventing or alleviating nausea or vomiting

Info

Publication number
JP2625457B2
JP2625457B2 JP33035687A JP33035687A JP2625457B2 JP 2625457 B2 JP2625457 B2 JP 2625457B2 JP 33035687 A JP33035687 A JP 33035687A JP 33035687 A JP33035687 A JP 33035687A JP 2625457 B2 JP2625457 B2 JP 2625457B2
Authority
JP
Japan
Prior art keywords
morphine
vomiting
anion
administered
kg
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 - Lifetime
Application number
JP33035687A
Other languages
Japanese (ja)
Other versions
JPS6468376A (en
Inventor
レオン・アイ・ゴールドバーグ
Original Assignee
ザ・ユニバーシティ・オブ・シカゴ
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to US92470 priority Critical
Priority to US07/092,470 priority patent/US4861781A/en
Application filed by ザ・ユニバーシティ・オブ・シカゴ filed Critical ザ・ユニバーシティ・オブ・シカゴ
Publication of JPS6468376A publication Critical patent/JPS6468376A/en
Application granted granted Critical
Publication of JP2625457B2 publication Critical patent/JP2625457B2/en
Anticipated expiration legal-status Critical
Application status is Expired - Lifetime legal-status Critical

Links

Description

【発明の詳細な説明】 発明の背景 モルヒネ及び他の臨床的に有用な麻酔性鎮痛剤の治療量の投与は消化器系統の不快な副作用をしばしば伴う。 DETAILED DESCRIPTION OF THE INVENTION Clinically administration of a therapeutic amount of useful narcotic analgesics background morphine and other invention involves the unpleasant side effects of digestive system often.
例えば、モルヒネ、及びメパリジン及びメタドンのような関連するアヘン剤は小腸循環平滑筋の収縮を生ずることにより腸の易動度を妨げることがある。 For example, morphine and related opiates such as Meparijin and methadone may interfere with mobility of the intestine by causing contractions of the small intestine circulation smooth muscle.

また、モルヒネ及び関連する麻酔剤は吐気及び胃腸管の易動度の増加を誘因し、嘔吐を生ずることがある。 Further, morphine and related anesthetic to trigger an increase in the mobility of nausea and gastrointestinal tract, which may result in vomiting. これらの副作用は髄質の最後野における嘔吐のための化学受容器トリガ帯の直接刺激により生ずる。 These side effects caused by direct stimulation of chemoreceptor trigger zone for emesis in the area postrema of the medulla. [グットマン(Goodman)及びビールマン(Bilman)のファーマコロ [Pharma roller of Goodman (Goodman) and beer Man (Bilman)
ジカル・ベイシス・オブ・セラペウティクス(Pharmacol Radical-Basis Of Serapeutikusu (Pharmacol
ogical Basis of Therapeutics 、第502頁(第6版、198 ogical Basis of Therapeutics, pp. 502 (6th edition, 198
0年刊)]。 0 annual)]. 研究はモルヒネ及び他の麻酔剤が犬に嘔吐を生ずることを示している。 Study morphine and other narcotics have shown that cause vomiting in dogs. 例えば、ワング(Wang)及びグラビアーノ(Glaviano)のJPET第111巻、第329〜33 For example, 111th volume JPET Wang (Wang) and Gurabiano (Glaviano), a 329-33
4頁(9143)はモルヒネを12匹の犬に0.5mg/kgの量で静脈内へ投与すれば、平均2.4分以内に9匹の犬が嘔吐した。 If administered to 4 pages (9143) is intravenously in an amount of 0.5 mg / kg morphine 12 dogs, 9 dogs within an average 2.4 minutes was vomiting. (mg/kgは体重1kg当たりのモルヒネのミリグラム数をいう)。 (Mg / kg refers to milligrams of morphine per body weight 1 kg). 1.0mg/kgのモルヒネを13匹の犬の筋肉内へ投与した時に、平均時間3.5分以内にそれらの犬の12匹が嘔吐した。 Morphine 1.0 mg / kg when administered intramuscularly in 13 dogs, 12 animals of those dogs within an average time of 3.5 minutes was vomiting.

発明の概要 本発明者らの米国特許第4,176,186号明細書はノルオキシモルホンの第4級誘導体の投与による麻酔性鎮痛剤の使用に付随する腸固定の治療法を開示している。 SUMMARY The present inventors of U.S. Pat. No. 4,176,186 of the invention discloses a method for treating intestinal fixed associated with the use of narcotic analgesics by administering a quaternary derivative of noroxymorphone. 同じ化合物がこれらの薬剤の投与に付随する吐気及び嘔吐の予防的及び治療的処置にも有用であることを今般見出した。 The same compound was found now that it is also useful for prophylactic and therapeutic treatment of nausea and vomiting associated with administration of these agents.

本発明によれば、温血動物へのモルヒネ及び関連するアヘン剤、メパリジン、メタドン等の酔性鎮痛剤の使用に付随する吐気または嘔吐を防止または軽減するための薬剤において、一般式 According to the present invention, morphine and related opiates to warm-blooded animals, Meparijin, in agents for preventing or alleviating nausea or vomiting associated with the use of drunk analgesics such as methadone, formula (式中、Rはアリル、クロルアリル、シクロプロピル− (Wherein, R allyl, Kuroruariru, cyclopropyl -
メチルまたはプロパルギ基であり、Xは酸のアニオンである) で表される少なくとも1種の化合物を有効成分とする温血動物に麻酔性鎮痛剤の使用に付随する吐気または嘔吐を防止または軽減するための薬剤が提供される。 A methyl or Puroparugi group, X is to prevent or alleviate nausea or vomiting associated with the use of narcotic analgesics in warm-blooded animals comprising as an active ingredient at least one compound represented by the anion of acid) there is provided a medicament for. xの好適な例は塩素アニオン、臭素アニオン、ヨウ素アニオンまたはメチルサルフェートアニオンかなる群から選ばれるアニオンである。 Suitable examples of x is an anion selected from chloride anion, bromine anion, iodine anion or methylsulfate anion Canal group.

上記一般式で表されるメチルナルトレクソン(上記一般式におけるRはシクロプロピル−メチル基である)またはノルオキシモルホンの他の第4級誘導体は麻酔性鎮痛剤を投与する前または投与と同時に動物へ投与する。 (R is cyclopropyl in the formula - is a methyl group) methyl naltrexone represented by the general formula or other quaternary derivatives of noroxymorphone simultaneously with or prior to administration to administer narcotic analgesics It is administered to an animal.
上述の化合物は腸内または腸管外に投与することができる。 The above compounds can be administered outside the intestinal or parenteral. 上述の化合物によるアヘン剤の鎮痛活性の妨害は何等観察されなかった。 Interference with the analgesic activity of opiates by the compounds described above was observed all.

本明細書で使用する術語「モルヒネ」とは他の意義に使用する旨の記載がない限り麻酔性鎮痛剤をいう。 The term "morphine" as used herein refers to a narcotic analgesic unless describes that used for other significance.

詳細な記載 本発明は温血動物へのモルヒネの投与に付随する吐気及び嘔吐を防止または軽減するためのノルオキシモルホンの第4級誘導体系薬剤に関する。 DETAILED DESCRIPTION The present invention relates to quaternary derivative drugs of noroxymorphone for preventing or alleviating nausea and vomiting associated with administration of morphine to warm-blooded animals.

上記薬剤として有用な化合物は下記の一般式により表される。 Compounds useful as the agent is represented by the following general formula.

式中、Rはアリル基、クロロアリル基、シクロプロピル−メチル基またはプロパルギル基であり、Xは酸のアニオン、特に塩素アニオン、臭素アニオン、ヨウ素アニオンまたはメチルサルフェートアニオンである。 Wherein, R allyl, chloroallyl group, cyclopropyl - methyl or propargyl group, X is an anion of an acid, in particular chlorine anion, bromine anion, iodine anion or methylsulfate anion.

上述の化合物は米国特許第4,176,186号明細書に記載されているようにして合成される。 The above compounds are synthesized as described in U.S. Patent No. 4,176,186. 特に好適なノルオキシモルホン誘導体はメチルナルトレクソンであるが、上述の一般式により表される他の化合物もまた適当である。 Particularly preferred noroxymorphone derivative is methyl naltrexone, other compounds represented by the above general formula are also suitable.

メチルナルトレクソンまたは他のノルオキシモルホン誘導体は患者の腸内または腸管外に投与することができる。 Methyl naltrexone or other noroxymorphone derivatives may be administered in enteral or parenteral patient. しかし、投与の好適な方法は注射である。 However, it is preferred methods injection administration. モルヒネを1回投与した後でさえ、吐気及び嘔吐は薬剤が起こる。 Even after administration of morphine once, nausea and vomiting drug occurs. しかし、モルヒネを慢性的に反復して使用すると通常腸の固定を生ずることがある。 However, it may produce a fixed normal intestinal Using morphine chronically repeated. 従って、モルヒネを外科手術または他の場合の激しい傷みを治療するために使用する場合にはモルヒネを投与前にメチルナルトレクソンの注射を受けることが意図される。 Therefore, when used to treat severe pain when surgery or other morphine are intended to receive an injection of methyl naltrexone before morphine.

以下の対照例及び実施例により説明するように、モルヒネと同時にまたはモルヒネを投与する前にメチルナルトレクソンを投与すれば、メチルナルトレクソンは嘔吐を抑制することを本発明は示す。 As illustrated by the following Reference Example and Examples, by administering a methyl naltrexone before administering simultaneously or morphine and morphine, methyl naltrexone present invention to suppress vomiting indicate. メチルナルトレクソンまたは他の第4級ノルオキシモルホン誘導体はモルヒネの投与前2時間までに投与することができる。 Methyl naltrexone or other quaternary noroxymorphone derivatives may be administered up to 2 hours before the administration of morphine. 期間は変化させることができること考えられる。 Period is considered to be able to be varied. 本発明においては、メチルナルトレクソンは注射器により筋肉内に投与された。 In the present invention, it was administered intramuscularly by methyl naltrexone syringe. また、メチルナルトレクソンは他の手段により腸内または腸管外に投与することができる。 Further, methyl naltrexone can be administered outside the intestinal or parenteral by other means. 投与されるモルヒネ1mg/kg毎に約0.05mg/kg〜約1.0mg/kgの範囲内の投与量で有効であることが見出された。 It was found to be effective at a dose in the range of about 0.05 mg / kg to about 1.0 mg / kg for each morphine 1 mg / kg administered. モルヒネと同じ注射器で投与する場合及びモルヒネの投与前約1時間までに投与する場合において有効であることが見出された。 It was found to be effective when administered before administration about 1 hour prior to when and morphine administered by the same syringe as morphine.

モルヒネの催吐性を逆転するためのメチルナルトレクソンの効果を以下に説明する。 The effect of methyl naltrexone for reversing the emetic of morphine will be described below. 単位mg/kgは体重1kg当たりの投与される物質のミリグラム数に関する。 Units mg / kg is about the number of milligrams of administered substances per body weight 1 kg.

対照例1及び実施例1 モルヒネ1mg/kgを5匹の犬の筋肉内へ投与した。 Control Example 1 and Example 1 Morphine 1 mg / kg was administered to five dogs in the muscles. 4匹の犬が嘔吐した。 4 dogs were vomiting. 個々の例において、嘔吐は4分以内に生じた。 In each example, vomiting occurred within four minutes. 異なる日に、同量のモルヒネを1mg/kgのメチルナルトレクソンと共にを同じ注射器で同じ5匹の犬の筋肉内へ投与した。 On different days, they were administered the same amount of morphine with methyl naltrexone of 1 mg / kg in the same syringe intramuscularly same five dogs. 嘔吐する犬はなかった。 Dog to vomit did not.

対照例2及び実施例2 6匹の犬に投与量1mg/kgのモルヒネを筋肉内に投与した。 Morphine dose 1 mg / kg in Control Example 2 and Example 2 6 dogs were administered intramuscularly. 6匹の全ての犬が嘔吐した。 All dogs of six was vomiting. 1日後、同量のモルヒネを0.5mg/kgのメチルナルトレクソンとを併用し、同じ注射器で同じ犬に投与した。 After one day, the same amount of morphine in combination with methyl naltrexone of 0.5 mg / kg, was administered in the same syringe to the same dogs. 嘔吐した犬はなかった。 Vomiting the dog did not.

対照例3及び実施例3 3匹の犬の1mg/kgのモルヒネを筋肉内に投与した。 Control Example 3 and Example 3 of 3 dogs 1 mg / kg of morphine was administered intramuscularly. 3
匹の全ての犬が嘔吐した。 All of the dogs of the animals was vomiting. 1日後、モルヒネを0.25mg/k One day later, the morphine 0.25mg / k
gのメチルナルトレクソンとを併用し、同じ注射器で投与した。 Together g of methyl naltrexone in, administered at the same syringe. 嘔吐した犬はなかった。 Vomiting the dog did not.

対照例4及び実施例4 メチルナルトレクソンを1mg/kgのモルヒネを投与する前に2匹の犬に投与した。 Control Example 4 and Example 4 Methyl naltrexone was administered to two dogs prior to administering the morphine 1 mg / kg. 1匹の犬にはモルヒネ投与の Of morphine administered to one dog
15分前に0.5mg/kgのメチルナルトレクソンを投与した。 15 minutes before the administration of methylnaltrexone complexone of 0.5 mg / kg.
嘔吐はなかった。 Vomiting was not. 2匹目の犬には、同量のメチルナルトレクソンをモルヒネ投与の30分前に投与した。 The two dogs eyes of a dog, was administered the same amount of methyl naltrexone to 30 minutes before the administration of morphine. 嘔吐は生じなかった。 Vomiting did not occur. 異なる日に、同じ犬にメチルナルトレクソンを投与しないで1.0mg/kgのモルヒネを投与したところ2匹の犬とも嘔吐した。 On different days, I was vomiting Both dogs were administered morphine 1.0mg / kg not administered methyl naltrexone to the same dog.

対照例5及び実施例5 1.0mg/kgのモルヒネを投与する1分前に4匹の犬の筋肉内へメチルナルトレクソン0.05mg/kgを投与した。 To Reference Example 5 and Example 5 1.0 mg / kg morphine in 1 minute before administration of the 4 dogs intramuscular administration methyl naltrexone 0.05 mg / kg. 全ての犬に嘔吐は生じなかった。 Vomiting did not occur in all dogs. 異なる日に、同じ犬をメチルナルトレクソンの投与なしに1.0mg/kgのモルヒネを投与した。 On different days, it was administered morphine 1.0mg / kg the same dog without the administration of methyl naltrexone. 4匹の犬は全て嘔吐した。 4 dogs were all vomiting.

メチルナルトレクソンのみの投与は動物に顕著な影響を生じないことが見出された。 Administration of methyl naltrexone alone were found to have no noticeable effect on the animal. 比較的多量の投与量のメチルナルトレクソンを用いるこれまでの研究は第4級ではないナルトレクソンとは異なり、メチルナルトレクソンは耐モルヒネ性薬剤の沈澱物回収系統ではないことを証明するものであった。 Unlike relatively large doses of methyl naltrexone Previous studies using a quaternary non-naltrexone, it is one which proves that it is not a precipitate recovery system of methyl naltrexone is resistant morphine agents It was. ルセール(Russell)らのEur. Ruseru (Russell) et al., Eur.
J.Pharmacol.第78巻、第255〜261頁(1982年)。 J.Pharmacol. 78, pp. 255-261 (1982). メチルナルトレクソンはモルヒネまたは麻酔剤の鎮痛活性を妨害しないことが見出された。 Methyl naltrexone was found not to interfere with the analgesic activity of morphine or narcotics.

Claims (3)

    (57)【特許請求の範囲】 (57) [the claims]
  1. 【請求項1】温血動物への麻酔性鎮痛剤の使用に付随する吐気または嘔吐を防止または軽減するための薬剤において、一般式 1. A drug for preventing or alleviating nausea or vomiting associated with the use of narcotic analgesics to warm-blooded animals, the formula (式中、Rはアリル、クロルアリル、シクロプロピル− (Wherein, R allyl, Kuroruariru, cyclopropyl -
    メチルまたはプロパルギ基であり、Xは酸のアニオンである) で表される少なくとも1種の化合物を有効成分とする温血動物への麻酔性鎮痛剤の使用に付随する吐気または嘔吐を防止または軽減するための薬剤。 A methyl or Puroparugi group, X is prevent or reduce nausea or vomiting associated with the use of narcotic analgesics in warm-blooded animals comprising as an active ingredient at least one compound represented by the anion of acid) drugs for.
  2. 【請求項2】Xが塩素アニオン、臭素アニオン、ヨウ素アニオンまたはメチルサルフェートアニオンかなる群から選ばれる特許請求の範囲第1項記載の薬剤。 Wherein X is a chlorine anion, bromine anion, iodine anion or methylsulfate anion canal Claims agent as set forth in claim 1, wherein selected from the group.
  3. 【請求項3】化合物がメチルナルトレクソンからなる特許請求の範囲第1項記載の薬剤。 3. A compound agent as set forth in claim 1, wherein the claims consisting of methyl naltrexone.
JP33035687A 1986-03-07 1987-12-28 Agents for preventing or alleviating nausea or vomiting Expired - Lifetime JP2625457B2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US92470 1987-09-03
US07/092,470 US4861781A (en) 1986-03-07 1987-09-03 Quaternary derivatives of noroxymorphone which relieve nausea and emesis

Publications (2)

Publication Number Publication Date
JPS6468376A JPS6468376A (en) 1989-03-14
JP2625457B2 true JP2625457B2 (en) 1997-07-02

Family

ID=22233375

Family Applications (1)

Application Number Title Priority Date Filing Date
JP33035687A Expired - Lifetime JP2625457B2 (en) 1986-03-07 1987-12-28 Agents for preventing or alleviating nausea or vomiting

Country Status (5)

Country Link
JP (1) JP2625457B2 (en)
CA (1) CA1315689C (en)
DK (1) DK167340B1 (en)
NZ (1) NZ222911A (en)
PH (1) PH22582A (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7563899B2 (en) 2005-05-25 2009-07-21 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US7674904B2 (en) 2005-05-25 2010-03-09 Progenics Pharmaceuticals, Inc. Synthesis of R-N-methylnaltrexone
US8247425B2 (en) 2008-09-30 2012-08-21 Wyeth Peripheral opioid receptor antagonists and uses thereof
US8338446B2 (en) 2007-03-29 2012-12-25 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US8471022B2 (en) 2008-02-06 2013-06-25 Progenics Pharmaceuticals, Inc. Preparation and use of (R),(R)-2,2′-bis-methylnaltrexone
US8546418B2 (en) 2007-03-29 2013-10-01 Progenics Pharmaceuticals, Inc. Peripheral opioid receptor antagonists and uses thereof
US8552025B2 (en) 2003-04-08 2013-10-08 Progenics Pharmaceuticals, Inc. Stable methylnaltrexone preparation
US9102680B2 (en) 2007-03-29 2015-08-11 Wyeth Llc Crystal forms of (R)-N-methylnaltrexone bromide and uses thereof

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6274591B1 (en) 1997-11-03 2001-08-14 Joseph F. Foss Use of methylnaltrexone and related compounds
US6451806B2 (en) 1999-09-29 2002-09-17 Adolor Corporation Methods and compositions involving opioids and antagonists thereof
US6469030B2 (en) 1999-11-29 2002-10-22 Adolor Corporation Methods for the treatment and prevention of ileus
US8518962B2 (en) 2005-03-07 2013-08-27 The University Of Chicago Use of opioid antagonists
US9662325B2 (en) 2005-03-07 2017-05-30 The University Of Chicago Use of opioid antagonists to attenuate endothelial cell proliferation and migration
US8524731B2 (en) 2005-03-07 2013-09-03 The University Of Chicago Use of opioid antagonists to attenuate endothelial cell proliferation and migration
CN104248763A (en) 2005-03-07 2014-12-31 芝加哥大学 Use of opioid antagonists to attenuate endothelial cell proliferation and migration
CA2625495A1 (en) * 2005-10-11 2007-04-19 Toray Industries, Inc. Therapeutic agent for nausea and/or vomiting
CN101827819B (en) * 2007-08-09 2013-06-12 伦斯勒理工学院 Quaternary opioid carboxamides
US8685995B2 (en) 2008-03-21 2014-04-01 The University Of Chicago Treatment with opioid antagonists and mTOR inhibitors

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9669096B2 (en) 2003-04-08 2017-06-06 Progenics Pharmaceuticals, Inc. Stable pharmaceutical formulations of methylnaltrexone
US8552025B2 (en) 2003-04-08 2013-10-08 Progenics Pharmaceuticals, Inc. Stable methylnaltrexone preparation
US9597327B2 (en) 2005-05-25 2017-03-21 Progenics Pharmaceuticals, Inc. Synthesis of (R)-N-methylnaltrexone
US7674904B2 (en) 2005-05-25 2010-03-09 Progenics Pharmaceuticals, Inc. Synthesis of R-N-methylnaltrexone
US8003794B2 (en) 2005-05-25 2011-08-23 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US8343992B2 (en) 2005-05-25 2013-01-01 Progenics Pharmaceuticals, Inc. Synthesis of R-N-methylnaltrexone
US8916581B2 (en) 2005-05-25 2014-12-23 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US7563899B2 (en) 2005-05-25 2009-07-21 Progenics Pharmaceuticals, Inc. (S)-N-methylnaltrexone
US8853232B2 (en) 2007-03-29 2014-10-07 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US9102680B2 (en) 2007-03-29 2015-08-11 Wyeth Llc Crystal forms of (R)-N-methylnaltrexone bromide and uses thereof
US8546418B2 (en) 2007-03-29 2013-10-01 Progenics Pharmaceuticals, Inc. Peripheral opioid receptor antagonists and uses thereof
US8338446B2 (en) 2007-03-29 2012-12-25 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US8772310B2 (en) 2007-03-29 2014-07-08 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US9879024B2 (en) 2007-03-29 2018-01-30 Progenics Pharmaceuticals., Inc. Crystal forms of (R)-N-methylnaltrexone bromide and uses thereof
US8471022B2 (en) 2008-02-06 2013-06-25 Progenics Pharmaceuticals, Inc. Preparation and use of (R),(R)-2,2′-bis-methylnaltrexone
US8916706B2 (en) 2008-02-06 2014-12-23 Progenics Pharmaceuticals, Inc. Preparation and use of (R),(R)-2,2′-bis-methylnaltrexone
US8822490B2 (en) 2008-09-30 2014-09-02 Wyeth Llc Peripheral opioid receptor antagonists and uses thereof
US9180125B2 (en) 2008-09-30 2015-11-10 Wyeth, Llc Peripheral opioid receptor antagonists and uses thereof
US9492445B2 (en) 2008-09-30 2016-11-15 Wyeth, Llc Peripheral opioid receptor antagonists and uses thereof
US8420663B2 (en) 2008-09-30 2013-04-16 Wyeth Peripheral opioid receptor antagonists and uses thereof
US8247425B2 (en) 2008-09-30 2012-08-21 Wyeth Peripheral opioid receptor antagonists and uses thereof
US9724343B2 (en) 2008-09-30 2017-08-08 Wyeth, Llc Peripheral opioid receptor antagonists and uses thereof
US8455644B2 (en) 2008-09-30 2013-06-04 Wyeth Peripheral opioid receptor antagonists and uses thereof

Also Published As

Publication number Publication date
CA1315689C (en) 1993-04-06
DK693387A (en) 1989-03-04
DK167340B1 (en) 1993-10-18
NZ222911A (en) 1990-11-27
PH22582A (en) 1988-10-17
JPS6468376A (en) 1989-03-14
DK693387D0 (en) 1987-12-30

Similar Documents

Publication Publication Date Title
Uhrbrand et al. Reversible and irreversible dyskinesia after treatment with perphenazine, chlorpromazine, reserpine and electroconvulsive therapy
Le Bars et al. Morphine blocks descending pain inhibitory controls in humans
Ramoska et al. A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment
EP1047426B1 (en) Use of methylnaltrexone and related compounds
CN1083264C (en) Pharmaceutical compositions comprising an opiate ant agonist and calcium salts, their use for the treatment of endorphin-mediated pathlogies
Rimback et al. Treatment of postoperative paralytic ileus by intravenous lidocaine infusion
DE69634609T2 (en) agonist analgesic synergy by simultaneous administration of subanalgesischen doses of mu-opioid and a kappa - agonists 2 opioi
EP0144243B1 (en) Analgesic compositions
Thomas Opioid-induced bowel dysfunction
EP0751766B1 (en) Nasal and ocular administration of ketamine to manage pain and for detoxification
US20030118641A1 (en) Abuse-resistant sustained-release opioid formulation
US6608073B1 (en) Intranasal codeine for the rapid suppression of cough and rapid relief of pain
US7968119B2 (en) Tamper-proof narcotic delivery system
Nachman et al. Learned taste aversions in rats as a function of dosage, concentration, and route of administration of LiCl
CN100431543C (en) Pharmaceutical composition
Costall et al. Emesis induced by cisplatin in the ferret as a model for the detection of anti-emetic drugs
EP0158532B1 (en) Use of 4-amino-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-2-methoxybenzamide for the manufacture of a medicament having anti-emetic activity.
Covell et al. Chemotherapy of malaria
Citron et al. Safety and efficacy of continuous intravenous morphine for severe cancer pain
US20040024006A1 (en) Opioid pharmaceutical compositions
Pentel et al. Asystole complicating physostigmine treatment of tricyclic antidepressant overdose
US20030211157A1 (en) Semi-sol delivery blend for water soluble molecules
DK160914B (en) Analgesic drug for parenteral or sublingual application
Eddy et al. The analgesic equivalence to morphine and relative side action liability of oxymorphone (4-hydroxydihydromorphinone)
JPH11505547A (en) Non smoking treatment with naltrexone and related compounds

Legal Events

Date Code Title Description
R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

EXPY Cancellation because of completion of term
FPAY Renewal fee payment (prs date is renewal date of database)

Year of fee payment: 11

Free format text: PAYMENT UNTIL: 20080411