Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-10-25
1998-05-19
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514303, 514381, 514394, 514397, 514417, A61K 3154, A61K 3144, A61K 3141, A61K 31415, A61K 3140
Patent
active
057536511
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a method of modifying Angiotensin II subtype 1 (AT.sub.1) receptor activity for the treatment of premenstrual syndrome (PMS) and for the mediation and alleviation of pain. More specifically, the present invention relates to the use of AT.sub.1 antagonists to modulate sympathetic nerve activity as treatment for pain and as treatment for PMS.
BACKGROUND OF THE INVENTION
The nervous system of the human body carries information in the form of nerve impulses to and from all parts of the body in order to regulate body activity. The nervous system consists of the central nervous system (CNS), including the brain and the spinal cord, which is responsible for integrating all activities of the nervous system; and the peripheral nervous system, including the cranial nerves and the spinal nerves, which link the receptors and the effector organs with the brain and spinal cord. The autonomic nervous system controls many bodily functions that are not consciously directed. The autonomic nervous system is subdivided into the sympathetic and the parasympathetic nervous systems, which individually control and coordinate various functions of body organs.
It is well known that the hypothalamus is an area of the brain which integrates hormonal and autonomic activity within the body, and coordinates physiological, behavioral and mood responses. The hypothalamus is the major central controller of the autonomic nervous system. Nearly every region of the brain sends signals to the hypothalamus. Pathways of nerve fibers descend from the brain and connect through synapses with areas on the brain stem, and then descend to the spinal cord where they synapse with neurons in the lateral columns of white matter which represent collections of nerve cells. There is an intimate interconnection between the nerve pathways involved in pain transmission and the sympathetic nervous system. (Basic Neurochemistry, Raven Press, 1994).
It is known that sympathetic functions and hypothalamic functions are partly regulated by AT.sub.1 receptors. It is also known that changing levels of ovarian hormones can modify the density and function of AT.sub.1 receptors, as well as induce changes in the morphology of nerve cells within the central nervous system.
At present, there are known to be two distinct Angiotensin II receptor subtypes: AT.sub.1 and AT.sub.2. Various drugs have been developed to block the receptor activity of the AT.sub.1 and AT.sub.2 receptors. Such drugs are commonly known as AT.sub.1 antagonists or AT.sub.2 antagonists, referring to the type of receptor which is being blocked.
U.S. Pat. No. 5,246,943 to Blankley et al. discloses novel AT.sub.2 antagonists which may have utility in treating numerous disorders including those associated with pain, and may have further utility in the regulation of the menstrual cycle. AT.sub.1 and AT.sub.2 receptors are distinct subtypes which have different functions. Blankley recognizes this and discloses a group of AT.sub.2 antagonists which have no AT.sub.1 antagonist properties.
U.S. Pat. No. 4,912,096 to Sudilovsky and U.S. Pat. No. 4,931,430 to Sudilovsky et al. disclose the use of ACE inhibitors as treatment for long term chronic and acute anxiety and depressive disorders. Such disorders are distinctly different from PMS in that they are typically long-term disorders which worsen in time and require long-term systemic medication. Symptoms associated with PMS, on the other hand are intermittent, occurring during the luteal phase of the menstrual cycle and with subsequent remission. Sudilovsky specifically addresses the enkephalinase inhibitory properties of ACE inhibitors and their effects on opiod receptor activity in treating depression and anxiety. Further, the Sudilovsky references do not suggest the use of AT.sub.1 antagonists.
PMS can have a debilitating effect on humans, through a variety of symptoms including changes in libido, erratic behavior, lack of emotional control, tension, mood swings, restlessness, insomnia, feelings of guil
REFERENCES:
patent: 4912096 (1990-03-01), Sudilovsky
patent: 4931430 (1990-06-01), Sudilovsky
patent: 5246943 (1993-09-01), Blankley et al.
"Basic Neurochemistry--Molecular, Cellular, and Medical Aspects"--5th Edition, 1994; pp. 608-611.
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"The Premenstrual Syndrome--Effects of Medical Ovariectomy"; Ken N. Muse, M.D., Nancy S. Cetel, M.D., Lori A. Futterman, Ph.D., and Samuel S.C. Yen, M.D., D.Sc; vol. 311, No. 21; pp. 1345-1349 (1984).
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