Title:
5-HT3 ANTAGONISTS FOR TREATMENT OF NAUSEA, BRADYCARDIA OF HYPOTENSION ASSOCIATED WITH MYOCARDIAL INSTABILITY
Document Type and Number:
WIPO Patent Application WO1991009593
Kind Code:
A3
Abstract:
A method for the treatment and/or prophylaxis of nausea and bradycardia and/or hypotension associated with myocardial instability in mammals, such as humans, which method comprises administering to the mammal in need of such treatment and/or prophylaxis an effective and/or prophylactic amount of a 5-HT3 receptor antagonist, such as a compound of formula (I): X-A-R, or a pharmaceutically acceptable salt thereof, wherein X is a phenyl group or a monocyclic 5 or 6 membered heteroaryl group, either of which group is optionally fused to a saturated or unsaturated 5-7 membered carbocyclic or heterocyclic ring; A is a linking moiety; and R is a saturated azabicyclic moiety or an imidazolyl moiety.
Inventors:
JOHNSON EDWARD STEWART (GB)
HAMILTON THOMAS CONWAY (GB)
HAMILTON THOMAS CONWAY (GB)
Application Number:
PCT/GB1990/001996
Publication Date:
September 05, 1991
Filing Date:
December 20, 1990
Export Citation:
Assignee:
BEECHAM GROUP PLC (GB)
International Classes:
A61K31/40; A61K31/00; A61K31/403; A61K31/415; A61K31/4184; A61K31/435; A61P1/08; A61P9/02; A61P9/04; A61P43/00; C07D209/52; C07D231/14; C07D231/38; C07D235/26; C07D451/04; C07D451/12; C07D451/14; C07D453/02; C07D453/06; C07D471/04; (IPC1-7): A61K31/00
Foreign References:
| EP0294292A2 | 1988-12-07 | |||
| EP0276163A2 | 1988-07-27 | |||
| EP0315390A2 | 1989-05-10 | |||
| EP0336759A1 | 1989-10-11 | |||
| EP0378111A1 | 1990-07-18 | |||
| DE3810552A1 | 1989-10-19 | |||
| DE3740984A1 | 1989-06-15 | |||
| EP0306323A2 | 1989-03-08 | |||
| EP0269452A2 | 1988-06-01 | |||
| EP0350129A1 | 1990-01-10 | |||
| EP0266730A1 | 1988-05-11 | |||
| EP0247266A1 | 1987-12-02 | |||
| EP0200444A2 | 1986-11-05 | |||
| EP0376624A1 | 1990-07-04 | |||
| EP0322016A1 | 1989-06-28 | |||
| EP0315316A2 | 1989-05-10 | |||
| EP0351385A2 | 1990-01-17 | |||
| EP0373061A1 | 1990-06-13 | |||
| GB2152049A | 1985-07-31 | |||
| GB2125398A | 1984-03-07 | |||
| GB2153821A | 1985-08-29 | |||
| EP0191562A2 | 1986-08-20 | |||
| EP0219193A1 | 1987-04-22 | |||
| EP0210840A2 | 1987-02-04 |
Other References:
The Journal of Pharmacology and Experimental Therapeutics, vol. 252, no. 2, February 1990 (US) H. WIlson et al.: "5-Hydroxytrptamine3 receptors mediate tachycardia in conscious instrumented dogs", pages 683-688
Baillieres Clin. Gastroenterol., vol. 2, Nr. 1, January 1988 P.L.R. Andrews: "The neurophysiology ofvomiting", pages 141-168
J. Mol. Cell Cardiol., vol. 21, Suppl. 2, 1989; Congress Ann Arbor, Michigan, 14-18 May 1989; H. Kameda et al.: "Cardiac effect of novel serotonin receptor (5-HT3) antagonists in guinea pigs", page S115,
Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 339, Nr. 3, March 1989, Springer Verlag H. Bertold et al.: "Inhibition of the 5-HT-induced cardiogenic hypertensive chemsreflex by the selective 5-HT3 receptor antagonist ICS 205-930" pages 259-262
J. Mol. Cell Cardiol., vol. 21, Suppl. 2, 1989, Congress Ann Arbor, Michigan, 14-18 May 1989 H. Kameda et al.: "The effects of ICS 205-930. A new 5-HT3 receptor antagonist on responses of guinea pig atria page S188
Br. J. Pharmacol., vol. 94, Nr. 2, June 1988, The Macmillan Press Ltd A. Butler et al.: "Pharmacological prperties of GR38032F, a novel antagonist at 5-HT3 receptors", pages 397-412
Naunyn Schimedeberg's Archives of Pharmacology , vol. 335, Nr. 6, June 1987, Springer Verlag G. Scholtysik: "Evidence for inhibition by ICS 205-930 and stimulation by BRL 34915 of K+ conductance in cardiac muscle", pages 692-696
J. Auton. Pharmacol., vol. 6, Nr. 3, September 1986, D.W. Dalton et al.: "An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and doca salt hypertensive rats", pages 219-228
Clinical and Experimental Pharmacology and Physiology, vol. 17, Nr. 9, September 1990 (Australia) R.G. Eans et al.: "Characteristics of cardiovascular reflexes originating from 5-HT3 receptors in the heart and lungs of unanaesthetized rabbits", pages 665-679
The Journal of Pharmacology and Experimental Therapeutics, vol. 254, no. 1, July 1990 (US) M.L. Cohen et al.: "LY277359 Maleate: a potent and selecti e 5-HT3 receptor antagonist without gastropokineic activity", pages 350-355
The Journal of Pharmacology and Experimentsl Therapeutics, vol. 248, Nr. 1, January 1989 (US) M.L. Cohen et al.: Comparison of the 5-HT3 receptor antagonist properties of ICS 205-930, GR38032F and zacopride", pages 197-201
J. Pharm. Pharmacol., vol. 40, Nr. 8, August 1988 N.M. Barnes et al.: "Identification of 5-HT3 recognition sites in the ferret area postrema", pages 586-588
Journal of Cardiovascular Pharmacology, vol. 13, Nr. 4, April 1989, Raven Press Ltd (New York, US) C. E. Wright et al.: "5-Carboxamido-tryptamine elicites 5-HT2 and 5-HT3 receptor-mediated cardiovascular responses in the conscious rabbit: evidence for 5-ht release from platelets" pages 557-564
Baillieres Clin. Gastroenterol., vol. 2, Nr. 1, January 1988 P.L.R. Andrews: "The neurophysiology ofvomiting", pages 141-168
J. Mol. Cell Cardiol., vol. 21, Suppl. 2, 1989; Congress Ann Arbor, Michigan, 14-18 May 1989; H. Kameda et al.: "Cardiac effect of novel serotonin receptor (5-HT3) antagonists in guinea pigs", page S115,
Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 339, Nr. 3, March 1989, Springer Verlag H. Bertold et al.: "Inhibition of the 5-HT-induced cardiogenic hypertensive chemsreflex by the selective 5-HT3 receptor antagonist ICS 205-930" pages 259-262
J. Mol. Cell Cardiol., vol. 21, Suppl. 2, 1989, Congress Ann Arbor, Michigan, 14-18 May 1989 H. Kameda et al.: "The effects of ICS 205-930. A new 5-HT3 receptor antagonist on responses of guinea pig atria page S188
Br. J. Pharmacol., vol. 94, Nr. 2, June 1988, The Macmillan Press Ltd A. Butler et al.: "Pharmacological prperties of GR38032F, a novel antagonist at 5-HT3 receptors", pages 397-412
Naunyn Schimedeberg's Archives of Pharmacology , vol. 335, Nr. 6, June 1987, Springer Verlag G. Scholtysik: "Evidence for inhibition by ICS 205-930 and stimulation by BRL 34915 of K+ conductance in cardiac muscle", pages 692-696
J. Auton. Pharmacol., vol. 6, Nr. 3, September 1986, D.W. Dalton et al.: "An investigation into the mechanisms of the cardiovascular effects of 5-hydroxytryptamine in conscious normotensive and doca salt hypertensive rats", pages 219-228
Clinical and Experimental Pharmacology and Physiology, vol. 17, Nr. 9, September 1990 (Australia) R.G. Eans et al.: "Characteristics of cardiovascular reflexes originating from 5-HT3 receptors in the heart and lungs of unanaesthetized rabbits", pages 665-679
The Journal of Pharmacology and Experimental Therapeutics, vol. 254, no. 1, July 1990 (US) M.L. Cohen et al.: "LY277359 Maleate: a potent and selecti e 5-HT3 receptor antagonist without gastropokineic activity", pages 350-355
The Journal of Pharmacology and Experimentsl Therapeutics, vol. 248, Nr. 1, January 1989 (US) M.L. Cohen et al.: Comparison of the 5-HT3 receptor antagonist properties of ICS 205-930, GR38032F and zacopride", pages 197-201
J. Pharm. Pharmacol., vol. 40, Nr. 8, August 1988 N.M. Barnes et al.: "Identification of 5-HT3 recognition sites in the ferret area postrema", pages 586-588
Journal of Cardiovascular Pharmacology, vol. 13, Nr. 4, April 1989, Raven Press Ltd (New York, US) C. E. Wright et al.: "5-Carboxamido-tryptamine elicites 5-HT2 and 5-HT3 receptor-mediated cardiovascular responses in the conscious rabbit: evidence for 5-ht release from platelets" pages 557-564
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