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WO1992000735A1 - Ropinirole et domperidone utilises dans la preparation d'un medicament pour le traitement de la maladie de parkinson - Google Patents

Ropinirole et domperidone utilises dans la preparation d'un medicament pour le traitement de la maladie de parkinson Download PDF

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Publication number
WO1992000735A1
WO1992000735A1 PCT/GB1991/001121 GB9101121W WO9200735A1 WO 1992000735 A1 WO1992000735 A1 WO 1992000735A1 GB 9101121 W GB9101121 W GB 9101121W WO 9200735 A1 WO9200735 A1 WO 9200735A1
Authority
WO
WIPO (PCT)
Prior art keywords
ropinirole
domperidone
treatment
parkinson
disease
Prior art date
Application number
PCT/GB1991/001121
Other languages
English (en)
Inventor
Christian De Mey
Nadarajah Sree Haran
Original Assignee
Smith Kline & French Laboratories Limited
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
Application filed by Smith Kline & French Laboratories Limited filed Critical Smith Kline & French Laboratories Limited
Publication of WO1992000735A1 publication Critical patent/WO1992000735A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine

Definitions

  • the present invention relates to the dopamine D 2 - receptor antagonist, domperidone (5-chloro-1- [ 1- [ 3- (2 , 3- dihydro-2-oxo-1H-benzimidazol-1-yl) propyl] -4-piperidinyl ] - 1 , 3-dihydro-2H-benzimidazole-2-one) and the D 2 -receptor agonist ropinirole (4- [2-dipropylaminoethyl] -1 , 3-dihydro- 2H-indol-2-one) for use in the treatment of Parkinson' s disease .
  • Domperidone is a well established dopamine D 2 - receptor antagonist practically devoid of central effects.
  • Ropinirole is a novel non-phenolic indolone
  • the present invention therefore provides, in a first aspect, ropinirole and domperidone for use in the
  • domperidone placebo was administered followed 1 hour later by an active dose of 800 ⁇ g ropinirole (treatment PS) , on another, an active dose of 20 mg domperidone, with an active dose of 800 ⁇ g ropinirole 1 hour later (treatment DS) , and on a further occasion, an active dose
  • the treatment sequences were randomly allocated in a period-balanced within-subject cross-over study design.
  • the subjects were supine and resting for one hour before the administration of domperidone or placebo (time t 0).
  • Venous blood was sampled for assay of plasma
  • ropinirole before dosing, and at 30, 60, 90, 120, 150, 180, 240, 300, 360, 480 and 600 minutes, and at 24 hours after dosing.
  • Plasma concentrations of ropinirole were assayed by radioimmunoassay.
  • the antiserum used was raised in sheep to a diazo-derivative of ropinirole conjugated to bovine serum albumin and diluted 1:2500.
  • the assay was shown to have a lower limit of
  • Venous blood was sampled for assay of plasma
  • prolactin before dosing of domperidone, at 30 minutes after dosing of domperidone, at 60 minutes after dosing of domperidone (i.e. immediately prior to dosing of ropinirole) and at 60, 120, 180, 240, 300, 360, 480 and 600 minutes, and 24 hours after administration of
  • prolactin and catecholamines subsequent to dosing were transformed as changes from the pre-dosing observations.
  • Responses to standing were calculated as the postural change relative to the supine observations immediately prior to sitting and standing.
  • treatment DS treatment DS
  • treatment PS treatment PS
  • treatment DS ropinirole preceded by 20 mg domperidone
  • the postural symptoms occurred after approximately only 1 minute standing in 2/9 incidents after treatment PS, after 2 minutes in 2/9 cases, and at the end of 3 minutes standing in the remaining 5/9 incidents.
  • faintness was observed, with pallor, dizziness and sweatiness. Often the incidents were associated with yawning.
  • nausea was the main feature.
  • bradycardia The reactions were essentially postural in nature and rapidly transient after resuming the supine position. There was no indication of altered
  • Plasma prolactin thus was clearly stimulated by domperidone (treatment DP) and inhibited by ropinirole (treatment PS).
  • Cmax maximum observed plasma concentration ranged from 3.57 to 12.6 nmol/l (mean: 6.24) and from 3.48 to 13.4 nmol/l (mean: 7.05) for treatments PS and DS, respectively.
  • the 95% interval estimate of the true ratio DS/PS was 0.96 to 1.14.
  • the area under the time course of the quantifiable plasma concentrations, AUC ranged from 11.6 to 48.0 nmol.h/l (mean:26.7) and from 10.1 to 68.1
  • the invention provides the use of domperidone and ropinirole in the manufacture of a medicament for the treatment of Parkinson's disease, characterised in that the treatment comprises first the administration of domperidone followed by the ropinirole.
  • the present invention provides a medicament pack comprising at least one unit dose of domperidone and at least one unit dose of
  • ropinirole said pack being suitable for use in the administration of the two drugs as hereinbefore described.
  • Figure2 Time course of the median plasma concentrations of ropinirole for treatments PS: placebo + ropinirole, and DS: domperidone + ropinirole.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte au dompéridone, l'antagoniste de récepteur-D2 de dopamine, et au ropinirole, l'agoniste de récepteur-D2, utilisés dans le traitement de la maladie de Parkinson.
PCT/GB1991/001121 1990-07-09 1991-07-08 Ropinirole et domperidone utilises dans la preparation d'un medicament pour le traitement de la maladie de parkinson WO1992000735A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB909015095A GB9015095D0 (en) 1990-07-09 1990-07-09 Therapeutic method
GB9015095.4 1990-07-09

Publications (1)

Publication Number Publication Date
WO1992000735A1 true WO1992000735A1 (fr) 1992-01-23

Family

ID=10678840

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1991/001121 WO1992000735A1 (fr) 1990-07-09 1991-07-08 Ropinirole et domperidone utilises dans la preparation d'un medicament pour le traitement de la maladie de parkinson

Country Status (3)

Country Link
AU (1) AU8195091A (fr)
GB (1) GB9015095D0 (fr)
WO (1) WO1992000735A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993023035A3 (fr) * 1992-05-18 1994-03-03 Smithkline Beecham Plc Emploi de derives d'indolone dans le traitement de troubles de la memoire, du dysfonctionnement sexuel et de la maladie de parkinson
WO1997006786A1 (fr) * 1995-08-18 1997-02-27 R.P. Scherer Limited Compositions a dissolution rapide et administrees par voie orale, pour agonistes de la dopamine
US7927624B2 (en) 2000-04-14 2011-04-19 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0113964A1 (fr) * 1982-12-07 1984-07-25 Smithkline Beckman Corporation 4-Aminoalkyle-2(3H)-indolones
EP0299602A2 (fr) * 1987-05-21 1989-01-18 Smith Kline & French Laboratories Limited L'emploi de dérivés de l'indolone pour la fabrication de médicaments pour le traitement du parkinsonisme

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0113964A1 (fr) * 1982-12-07 1984-07-25 Smithkline Beckman Corporation 4-Aminoalkyle-2(3H)-indolones
EP0299602A2 (fr) * 1987-05-21 1989-01-18 Smith Kline & French Laboratories Limited L'emploi de dérivés de l'indolone pour la fabrication de médicaments pour le traitement du parkinsonisme

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
2ND INTERN. CONFER. PARKINSON. DIS. November 1989, KYOTO pages 581 - 584; J.M. BOTTOMLEY ET AL: 'PHARMACOLOGICAL ACTIVITY &101468) IN MAN ' see the whole document *
DRUGS OF THE FUTURE vol. 15, no. 8, 1990, pages 863 - 864; &F-101468 & ROPINIROLE ' see the whole document *
JOURNAL OF MEDICINAL CHEMISTRY vol. 28, no. 7, July 1985, pages 1533 - 1536; G. GALLAGHER ET AL: '4-(2-(DI-n-PROPYLAMINO)ETHYL)-2(3H)-INDOLONE: A PREJONCTIONAL DOPAMINE RECEPTOR AGONIST ' cited in the application see the whole document *
THE LANCET vol. 1, no. 8116, March 17, 1979, pages 570 - 572; Y. AGID ET AL: 'BROMOCRIPTINE ASSOCIATED WITH A PERIPHERAL DOPAMINE BLOCKING AGENT IN TREATMENT OF PARKINSON'DISEASE ' see the whole document *
THE LANCET vol. 1, no. 8652, June 24, 1989, pages 1445 - 1446; R. KAPOOR ET AL: 'TREATMENT OF PARKINSON'DISEASE &101468 ' see the whole document *
THE LANCET vol. 336, no. 8710, August 7, 1990, pages 316 - 317; M.J. VIDAILHET: 'ROPINIROLE WITHOUT LEVODOPA IN PARKINSON'DISEASE ' see the whole document *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993023035A3 (fr) * 1992-05-18 1994-03-03 Smithkline Beecham Plc Emploi de derives d'indolone dans le traitement de troubles de la memoire, du dysfonctionnement sexuel et de la maladie de parkinson
WO1997006786A1 (fr) * 1995-08-18 1997-02-27 R.P. Scherer Limited Compositions a dissolution rapide et administrees par voie orale, pour agonistes de la dopamine
US6316027B1 (en) 1995-08-18 2001-11-13 R. P. Scherer Technologies, Inc. Fast-dissolving dosage forms for dopamine agonists
US7927624B2 (en) 2000-04-14 2011-04-19 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
EP2343060A1 (fr) 2000-04-14 2011-07-13 Jagotec AG Comprimés à plusieurs couches et à une liberation controlée, qui contiennent une couche active et une ou plusieurs couches de barrière
US8303986B2 (en) 2000-04-14 2012-11-06 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
US8460706B2 (en) 2000-04-14 2013-06-11 Jagotec Ag Hydrophilic/lipophilic polymeric matrix dosage formulation
EP3175848A1 (fr) 2000-04-14 2017-06-07 Jagotec AG Comprimé à libération contrôlée multicouche comprenant une couche active et une ou plusieurs couches barrières

Also Published As

Publication number Publication date
AU8195091A (en) 1992-02-04
GB9015095D0 (en) 1990-08-29

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