Title:
ENDOTHELIN ANTAGONISTS AND ENDOTHELIN SYNTHASE INHIBITORS FOR THE PREVENTION AND TREATMENT OF UTERINE CONTRACTILITY DISORDERS, PREECLAMPSIA, ATHEROSCLEROTIC VASCULAR DISEASE, HYPERTENSION AND FOR HORMONE REPLACEMENT THERAPY
Document Type and Number:
WIPO Patent Application WO1996035453
Kind Code:
A3
Abstract:
A pharmaceutical composition for and methods of treatment of menstrual disorders, e.g., dysmenorrhea, in a non-pregnant female, preterm labor, preeclampsia and/or fetal growth retardation in a pregnant female mammal, treatment of atherosclerotic vascular disease and hypertension in males as well as females, and for hormone replacement therapy in peri- and post-menopausal females, comprising administering effective amounts of an endothelin antagonist and/or an endothelin synthase inhibitor or both, in combination with a progestin, and/or an estrogen, and/or a cyclooxygenase inhibitor, and/or a nitric oxide donor and/or nitric oxide substrate, to prevent and/or ameliorate said conditions, are disclosed. In the method aspects, the endothelin antagonist and/or endothelin synthase inhibitor can be administered alone for treatment of menstrual disorders, e.g., dysmenorrhea, in a non-pregnant female, preterm labor, preeclampsia and/or fetal growth retardation in a pregnant female mammal. Further, methods for screening compounds for such treatments are disclosed.
Inventors:
CHWAKISZ KRISTOF (DE)
GARFIELD ROBERT E (DE)
GARFIELD ROBERT E (DE)
Application Number:
PCT/US1995/015220
Publication Date:
March 13, 1997
Filing Date:
November 30, 1995
Export Citation:
Assignee:
CHWAKISZ KRISTOF (DE)
GARFIELD ROBERT E (DE)
GARFIELD ROBERT E (DE)
International Classes:
A61K31/00; A61K31/223; A61K31/42; A61K31/565; A61K31/57; A61K31/60; A61K38/12; A61K45/06; (IPC1-7): A61K45/06; A61K38/12; A61K31/57; A61K31/60; A61K31/565; A61K31/42; A61K31/22
Domestic Patent References:
| WO1995000537A1 | 1995-01-05 | |||
| WO1993025580A1 | 1993-12-23 | |||
| WO1993010144A1 | 1993-05-27 | |||
| WO1995002408A1 | 1995-01-26 | |||
| WO1995013802A1 | 1995-05-26 |
Foreign References:
| US5260276A | 1993-11-09 | |||
| US5378715A | 1995-01-03 |
Other References:
R.E. GARFIELD ET AL.: "Reversal of preeclampsia symptoms induced in rats by nitric oxide inhibition with L-arginine, steroid hormones and an endothelin antagonist", SOC. GYNECOL. INVEST., 1994, XP002015069
K. CHWALISZ ET AL.: "Estradiol inhibits the onapristone-induced preterm parturition in Guinea pigs by blocking cervical ripening", J SOC GYNECOL INVEST, vol. 2, no. 2, March 1995 (1995-03-01), pages 267, XP002015070
K. CHWALISZ ET AL.: "Role of progesterone during pregnancy: models of parturition and preeclampsia", Z GEBURTSHILFE PERINATOL, vol. 198, no. 5-5, 1994, pages 170 - 180, XP002015071
V. RICHARD ET AL.: "In vivo evidence of an endothelin-induced vasopressor tone after inhibition of nitric oxide synthesis in rats", CIRCULATION, vol. 91, no. 3, 1 February 1995 (1995-02-01), pages 771 - 775, XP002015072
C. YALLAMPALLI ET AL.: "Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia", AM J OBSTET GYNECOL, vol. 169, no. 5, 1993, pages 1316 - 1320, XP002015073
C.YALLAMPALLI ET AL.: "Uterine contractile responses to endothelin-1 and endothelin receptors are elevated during labor", BIOL REPROD, vol. 51, no. 4, 1994, pages 640 - 645, XP002015074
K. CHWALISZ ET AL.: "Estradiol inhibits the onapristone-induced preterm parturition in Guinea pigs by blocking cervical ripening", J SOC GYNECOL INVEST, vol. 2, no. 2, March 1995 (1995-03-01), pages 267, XP002015070
K. CHWALISZ ET AL.: "Role of progesterone during pregnancy: models of parturition and preeclampsia", Z GEBURTSHILFE PERINATOL, vol. 198, no. 5-5, 1994, pages 170 - 180, XP002015071
V. RICHARD ET AL.: "In vivo evidence of an endothelin-induced vasopressor tone after inhibition of nitric oxide synthesis in rats", CIRCULATION, vol. 91, no. 3, 1 February 1995 (1995-02-01), pages 771 - 775, XP002015072
C. YALLAMPALLI ET AL.: "Inhibition of nitric oxide synthesis in rats during pregnancy produces signs similar to those of preeclampsia", AM J OBSTET GYNECOL, vol. 169, no. 5, 1993, pages 1316 - 1320, XP002015073
C.YALLAMPALLI ET AL.: "Uterine contractile responses to endothelin-1 and endothelin receptors are elevated during labor", BIOL REPROD, vol. 51, no. 4, 1994, pages 640 - 645, XP002015074
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