Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-01-16
2002-09-17
Travers, Russell (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06451783
ABSTRACT:
FIELD OF THE INVENTION
The present invention provides methods of treating obesity, sexual dysfunction (including erectile dysfunction), diabetes, insulin resistance, hyperinsulinemia, Syndrome X, adrenal dysfunction, hypertension, hypercholesterolemia, atherosclerosis, hyperlipoproteinemia, hypertriglyceridemia, or substance abuse, the methods comprising the step of administering to a patient having or at risk of having one of the above-mentioned diseases or conditions a therapeutically effective amount of a compound that attenuates the binding of agouti-related protein to melanocortin receptors, but does not attenuate the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors.
The present invention also provides methods of identifying a compound that is useful for the treatment of obesity, sexual dysfunction (including erectile dysfunction), diabetes, insulin resistance, hyperinsulinemia, Syndrome X, adrenal dysfunction, hypertension, hypercholesterolemia, atherosclerosis, hyperlipoproteinemia, hypertriglyceridemia, or substance abuse, the methods comprising the steps of: 1) determining if a compound affects the binding of agouti-related protein to melanocortin receptors; 2) determining if a compound affects the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors; and 3) selecting a compound that attenuates the binding of agouti-related protein to melanocortin receptors, but does not attenuate the binding of cc-melanocyte stimulating hormone to melanocortin receptors.
BACKGROUND OF THE INVENTION
Obesity is a devastating disease. In addition to harming physical health, obesity can wreak havoc on mental health because obesity affects self-esteem, which ultimately can affect a person's ability to interact socially with others. Unfortunately, obesity is not well understood, and societal stereotypes and presumptions regarding obesity only tend to exacerbate the psychological effects of the disease. Because of the impact of obesity on individuals and society, much effort has been expended to find ways to treat obesity, but little success has been achieved in the long-term treatment and/or prevention of obesity.
It has been discovered that overexpression of a protein called agouti-related protein (AGRP) results in obesity. Agouti-related protein has been shown to be a potent, selective, endogenous antagonist of melancortin-3 (MCR-3) and melanocortin-4 (MCR-4) receptors, which have been implicated in weight regulation. It has also been shown that ubiquitous expression of human AGRP in transgenic mice results in obesity. In contrast, &agr;-melanocyte stimulating hormone (&agr;-MSH) decreases feeding and is an endogenous agonist of MCR-4 and MCR-3. It is believed that the binding sites for &agr;-MSH and AGRP on melanocortin-4 receptors are different, but may partially overlap. In one embodiment, the present invention provides a method of identifying compounds useful to treat obesity, the compounds being selected from compounds that attenuate the binding of agouti-related protein to melanocortin receptors, but do not attenuate the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors.
Sexual dysfunction occurs in males and females and includes hypoactive sexual desire disorder, sexual anhedonia and dyspareunia. Hypoactive sexual desire disorder is a disorder in which sexual fantasies and desire for sexual activity are persistently or recurrently diminished or absent, causing marked distress or interpersonal difficulties. Symptoms and signs of hypoactive sexual desire disorder include the patient complaining of a lack of interest in sex, even in ordinarily erotic situations. The disorder is usually associated with infrequent sexual activity, often causing serious conflict between partners. Sexual anhedonia is decreased or absent pleasure in sexual activity. Sexual anhedonia is almost always classified under hypoactive sexual desire disorder, because loss of pleasure typically results in loss of desire. Dyspareunia is painful coitus or attempted coitus.
Erectile dysfunction is another example of a sexual dysfunction. Erectile dysfunction, like obesity, is another condition that can result in severe emotional distress. Persons suffering from erectile dysfunction are unable to develop and/or maintain an erection of the penis. Historically, erectile dysfunction has been viewed as having biological and psychological components, and more effort appeared to be exerted on treating the psychological components of the condition. Only recently with the introduction of Viagra® have persons having this condition been offered the hope of an oral medicinal treatment. In accordance with the teachings herein, compounds that attenuate the binding of agouti-related protein to melanocortin receptors, but do not attenuate the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors are useful to treat sexual dysfunction, including erectile dysfunction.
In addition to obesity and sexual dysfunction, compounds that attenuate the binding of agouti-related protein to melanocortin receptors, but do not attenuate the binding of &agr;-melanocyte stimulating hormone to melanocortin receptors are useful to treat diabetes, insulin resistance, hyperinsulinemia, Syndrome X, adrenal dysfunction, hypertension, hypercholesterolemia, atherosclerosis, hyperlipoproteinemia, hypertriglyceridemia, or substance abuse.
In spite of the early discovery of insulin and its subsequent widespread use in the treatment of diabetes, and the later discovery of and use of sulfonylureas, biguanides and thiazolidenediones, such as troglitazone, rosiglitazone or pioglitazone, as oral hypoglycemic agents, the treatment of diabetes remains less than satisfactory.
The use of insulin currently requires multiple daily doses, usually by self-injection. Determination of the proper dosage of insulin requires frequent estimations of the sugar in urine or blood. The administration of an excess dose of insulin causes hypoglycemia, with effects ranging from mild abnormalities in blood glucose to coma, or even death. Treatment of non-insulin dependent diabetes mellitus (Type II diabetes, NIDDM) usually consists of a combination of diet, exercise, oral hypoglycemic agents, e.g., thiazolidenediones, and, in more severe cases, insulin. However, the clinically available hypoglycemic agents can have side effects that limit their use, or an agent may not be effective with a particular patient. In the case of insulin dependent diabetes mellitus (Type I), insulin is usually the primary course of therapy. Hypoglycemic agents that have fewer side effects or succeed where others fail are needed.
Atherosclerosis, a disease of the arteries, is recognized to be a leading cause of death in the United States and Western Europe. The pathological sequence leading to atherosclerosis and occlusive heart disease is well known. The earliest stage in this sequence is the formation of “fatty streaks” in the carotid, coronary and cerebral arteries and in the aorta. These lesions are yellow in color due to the presence of lipid deposits found principally within smooth-muscle cells and in macrophages of the intima layer of the arteries and aorta. Further, it is postulated that most of the cholesterol found within the fatty streaks, in turn, give rise to development of “fibrous plaques,” which consist of accumulated intimal smooth muscle cells laden with lipid and are surrounded by extra-cellular lipid, collagen, elastin and proteoglycans. The cells plus matrix form a fibrous cap that covers a deeper deposit of cell debris and more extra-cellular lipid. The lipid is primarily free and esterified cholesterol. The fibrous plaque forms slowly, and is likely in time to become calcified and necrotic, advancing to a “complicated lesion,” which accounts for arterial occlusion and tendency toward mural thrombosis and arterial muscle spasm that characterize advanced atherosclerosis.
Epidemiological evidence has firmly established hyperlipidemia as a primary risk factor in causing cardiovascular disease (CVD) d
Hadcock John R.
Swick Andrew G.
Benson Gregg C.
Crissey Todd M.
Hui San-ming
Pfizer Inc.
Richardson Peter C.
LandOfFree
Treatments for obesity and methods for identifying compounds... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treatments for obesity and methods for identifying compounds..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treatments for obesity and methods for identifying compounds... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2877411