Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms

A technology of norepinephrine, epinephrine, used in the field of prevention and treatment of vasomotor disease

Inactive Publication Date: 2005-12-07
WYETH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of this treatment can bring about a number of undesired side effects known in the art due to the high doses necessary to alleviate the hot flashes described herein

Method used

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  • Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms
  • Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms
  • Use of norepinephrine reuptake modulators for preventing and treating vasomotor symptoms

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Experimental program
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Effect test

Embodiment 1

[0135] In preclinical models of vasomotor instability, NRIs are effective in attenuating vasomotor instability Fixed effect

[0136] The method described in the morphine-dependent rat model in the General Methods section was used except that the rats were injected subcutaneously with vehicle (sterile water) or desipramine 1 hour before administration of naloxone. ), the desipramine can be prepared as described in US Patent Publication No. 2002 / 0107249, dissolved in sterile water and administered at 0.1, 1.0, 10 and 30 mg / kg ( image 3 A). Desipramine dose-dependently attenuated naloxone-induced hot flashes at the site of maximal hot flashes (15 minutes after naloxone administration; Δ°C, mean + SEM).

[0137] Subcutaneous injection of vehicle (sterile water) or desipramine (dissolved in sterile water and administered at 10 mg / kg) to rats ( image 3 B). In a telemetry model of OVX-induced thermoregulatory disturbances, changes in TST over time (Δ°C, mean + SEM) demonstra...

Embodiment 2

[0142] Alleviating effect of NRI combined with SRI on vasomotor instability

[0143]The method described in the morphine-dependent rat model in the General Methods section was used except that the rats were injected subcutaneously with vehicle (sterile water), desipramine 1 hour before administration of naloxone ) (prepared as described in US-A-3,454,554, dissolved in sterile water and administered at 0.1, 1.0, 10 mg / kg) or fluoxetine (fluoxetine) (Sigma, dissolved in sterile water, administered at 10, 30 , 60 mg / kg administration), or a combination of fluoxetine at 10 mg / kg and desipramine in increasing doses as listed above.

[0144] At the point of maximum hot flashes (15 minutes after naloxone administration; Δ°C, mean + SEM), desipramine dose-dependently attenuated naloxone-induced hot flashes in the MD model, but caused A slight slope of the evaluation line (solid line, Figure 4 ). The slight slope of the evaluation line is characteristic of compounds with multisit...

Embodiment 3

[0146] Alleviation of vasomotor instability by compounds with dual NRI / SRI activity

[0147] The method described in the morphine-dependent rat model in the General Methods section was adopted, except that the rats were subcutaneously injected with vehicle (sterile water), venlafaxine ( venlafaxine) (dissolved in sterile water and administered at 1.0, 10, 20, 40 mg / kg) or DVS-233 (dissolved in sterile water and administered at 1.0, 10, 30, 60 mg / kg). Venlafaxine and DVS-233 were synthesized as described in US-A-4,535,186. At the point of maximum hot flash (15 minutes after administration of naloxone; Δ°C, mean + SEM), venlafaxine dose-dependently (ED 50 Value = 15+7mg / kg) alleviated naloxone (naloxone)-induced hot flashes ( Figure 5 A). DVS-233 dose-dependently (ED 50 Value = 30+3mg / kg) alleviated naloxone (naloxone)-induced hot flashes ( Figure 5 B).

[0148] Figure 5 Methods for C and 5D were as described within the telemetry model in the general methods section....

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Abstract

The present invention relates to the use of compounds and composition of compounds that modulate norepinephrine levels for the prevention and treatment of vasomotor symptoms, such as hot flush, caused by, inter alia, thermoregulatory dysfunctions.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Application Serial No. 60 / 418,591, filed October 15, 2002, the disclosure of which is hereby incorporated by reference in its entirety. field of invention [0003] The present invention relates to the use of compounds and compound compositions for regulating norepinephrine levels in the prevention and treatment of vasomotor syndrome (VMS) and the like. Background of the invention [0004] Vasomotor syndrome (VMS), known as hot flashes and night sweats, is the most common symptom associated with menopause, occurring in 60% to 80% of women with natural or surgically induced menopause. VMS may be an adaptive response of the central nervous system (CNS) to sex steroid attenuation. To date, the most effective treatments for VMS are hormone-based treatments, including estrogens and / or some progestogens. Hormone therapy is very effective in relieving VMS, but it doesn't work for all wo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/13A61K31/55
Inventor 达莱尔·科莱曼·迪克尔伊斯特万·约瑟夫·梅尔肯塔勒利萨·利文撒尔金伯利·吉恩·赛普劳伦斯·托马斯·欧康纳
Owner WYETH LLC
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