Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-10-22
2000-12-19
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514910, 514321, 514657, 514716, 514909, A61K 31535, A61K 31445, A61K 31135, A61K 31075
Patent
active
061628050
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the treatment or prevention of obesity by the administration of a combination of a NK-1 receptor antagonist and a selective serotonin reuptake inhibitor.
Obesity is a chronic disease that is highly prevalent in modern society and is associated not only with a social stigma, but also with decreased life span and numerous medical problems, including adverse psychological development, reproductive disorders such as polycystic ovarian disease, dermatological disorders such as infections, varicose veins, Acanthosis nigricaits, and eczema, exercise intolerance, diabetes mellitus, insulin resistance, hypertension, hypercholesterolemia, cholelithiasis, osteoarthritis, orthopedic injury, thromboembolic disease, cancer, and coronary heart disease. Rissanen et al, British Medical Journal, 301:835-837 (1990).
Treatment regimens for obesity typically include the use of selective serotonin reuptake inhibitors (SSRIs). SSRIs alter the synaptic availability of serotonin through their inhibition of presynaptic reaccumulation of neuronally released serotonin. The SSRI, fluoxetine, has found to be of use in the treatment of obesity.
Neurokinin 1 (NK-1; substance P) receptor antagonists are being developed for the treatment of a number of physiological disorders associated with an excess or imbalance of tachykinins, and in particular substance P. Examples of such conditions include disorders of the central nervous system such as anxiety, depression and psychosis (see, for instance, International (PCT) patent specification Nos. WO 95/16679, WO 95/18124 and WO 95/23798).
International (PCT) patent specification No. WO 96/24353 published Aug. 15, 1996) claims methods for the treatment of psychiatric disorders using a combination of a tachykinin antagonist and a serotonin agonist or selective serotonin reuptake inhibitor referring inter alia to bulimia nervosa. However, the disclosure of WO 96/24353 does not provide any teaching as to whether the claimed combination has any efficacy and in particular there is no direction towards specific combinations which might treat obesity.
There is therefore a need for a combination of an SSRIs with a NK-1 receptor antagonist, which combination provides an unexpected and advantageous effect in treating obesity. Such combinations may for example provide an enhanced anti-obesity effect. They may also provide for a rapid onset of action to combat obesity thereby enabling prescription on an "as-needed" basis.
A particularly preferred class of NK-1 receptor antagonists of use in the present invention are those which are able to cross the blood-brain barrier otherwise known as CNS- or brain-penetrant compounds. CNS-penetrant NK-1 receptor antagonists have been found to potentiate the pharmacological effects of fluoxetine. While not being bound to any particular theory of operation, an enhanced effect at treating or preventing a psychological stress response in an animal assay is observed with the combination of drugs than would be expected from either drug alone. In particular, combination therapy of a CNS-penetrant NK-1 receptor antagonist and a selective serotonin reuptake inhibitor effectively inhibits separation-induced vocalisations in guinea-pig pups. Such unexpected results would not have been predicted based on the disclosures in the art.
The present invention accordingly provides the use of a NK-1 receptor antagonist and an SSRI for the manufacture of a medicament for the treatment or prevention of obesity.
The present invention also provides a method for the treatment or prevention of obesity, which method comprises administration to a patient in need of such treatment an amount of a NK-1 receptor antagonist and an amount of an SSRI, such that together they give effective relief.
In a further aspect of the present invention, there is provided a pharmaceutical composition for the treatment or prevention of obesity comprising a NK-1 receptor antagonist and an SSRI, together with at least one pharmaceutically acceptable carrier or excipient.
It will be appreciated
REFERENCES:
CA 105:218899, abstract of JP 61148121 A2, Jul. 1986.
CA 115:270439, Pijl et al., 1991.
CA 126:152744, Ricca et al., 1996.
Jordan Kimberly
Merck Sharp & Dohme Limited
Rose David L.
Thies J. Eric
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