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Methods and compositions for the treatment of neuropathies and related disorders

A compound, neurological technology, applied in the fields of botanical equipment and methods, animal repellents, plant growth regulators, etc., to solve problems that are not considered effective, etc.

Inactive Publication Date: 2008-09-24
DOV PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Multiple Drug Combinations Used to Control Neuropathic Symptoms Are Not Prescribed and Considered Effective in the Treatment of Nociceptive Pain

Method used

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  • Methods and compositions for the treatment of neuropathies and related disorders
  • Methods and compositions for the treatment of neuropathies and related disorders
  • Methods and compositions for the treatment of neuropathies and related disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0466] Bicifadine effectively reduces contact hyperalgesia and thermal hyperalgesia in a spinal nerve ligation model

[0467] Tight ligation of spinal nerves in mice induces hyperalgesia, allodynia, and spontaneous pain, thus providing an accepted model for neuropathic pain in humans. Male Sprague-Dawley rats Rj:SD (IOPS Han) weighing 218-260 g were anesthetized (sodium pentobarbital 40 mg / kg, i.p.) at the beginning of the experiment, and an incision was made at the L4-S2 position to expose the L5 and L6 left spinal nerves, which were tightly ligated (4-0 silk) distal to the dorsal root ganglion and anterior to the sciatic nerve, as per Kim and Chung( Pain , 50 : 355-363, 1992) by the method first described. Then the incision was sutured, and amoxicillin (100 mg / kg s.c.) was injected intramuscularly to the rat to heal the wound. At 4 weeks postoperatively, when the chronic pain state was fully stabilized, the rats were sequentially subjected to contact stimulation and th...

Embodiment 2

[0477] 1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane effectively reduces the contact hyperalgesia and heat hyperalgesia

[0478] In this example, another exemplary substituted 1-aryl-3-azabicyclo[3.1.0]hexane was evaluated for its efficacy in the spinal nerve ligation (Chung) model of neuropathic pain associated with neuropathy. capacity for symptoms. In this study, a polyaryl-substituted compound as described above was evaluated as described in Example 1 above: 1-(3,4-dichlorophenyl)-3-azabicyclo[3.1 .0] hexane. 1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane was administered orally at the indicated doses 60 minutes before testing and compared with the vehicle control group. Data were analyzed as described in Example 1 using paired and unpaired Student's t-test comparing responses of injured paws in the treated and vehicle control groups.

[0479] Respectively as image 3 and Figure 4 As shown, 1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane effectively in...

Embodiment 3

[0481] Bicifadine effectively relieves neuropathy symptoms in a rat model of streptozotocin-induced diabetes

[0482] At the beginning of the experiment, male Sprague Dawley rats Rj; SD (IOPSHan) weighing 218-260 g were used in this experiment to induce diabetes. They were divided into vehicle control group and streptozotocin-treated group. Throughout the experiment, the rats were kept in a room with controlled temperature (19.5-24.5°C) and relative humidity (45-65%), and a 12h light / dark cycle, and had free access to purified water and experimental standard particles feed.

[0483] On day 0, rats were injected intraperitoneally with streptozotocin (STZ; 75 mg / kg) to induce diabetes. On day 23, to confirm that the STZ-administered rats had developed diabetes, hyperglycemia was measured using blood glucose test strips. Animals with blood glucose concentrations below 250 mg / l were not used in further studies.

[0484] Bicifadine was administered at the indicated doses to a...

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Abstract

The present invention provides novel compositions and methods for treating symptoms associated with neuropathic disorders such as hyperalgesia, allodynia, and parasthesias, using a 1-aryl-3-azabicyclo[3.1.0] hexane. The invention further relates to the use of 1-aryl-3-azabicyclo[3.1.0] hexanes in pharmaceutical compositions and methods for treating neuropathic disorders and related symptoms in mammals. Patients amenable to treatment according to the invention include those suffering from diabetic neuropathies, post-herpetic neuralgia, trigeminal neuralgia, chronic lower back pain, sciatica, idiopathic and post-traumatic neuropathies, HIV-associated neuropathic pain, among many other neuropathic disorders and related symptoms.

Description

technical field [0001] The present invention relates to compositions and methods for treating neurological disorders and their associated symptoms, including neuropathic pain. Background technique [0002] The etiology of neurological disorders is often complex, and individuals with neuropathy often present with a variety of adverse symptoms. One of the most common and severe adverse symptoms occurring in neurological disorders is a condition commonly referred to as "neuropathic pain". Neuropathic pain has distinct neurological and sensory characteristics from acute nociceptive pain (eg, pain caused by burns or surgical incisions), which make neuropathic pain difficult to treat with standard treatments for nociceptive pain. [0003] Distinct neurological and sensory features that characterize a neurological disorder may include, but are not limited to, allodynia (a painful response to a nonnoxious stimulus such as touching clothing), hyperalgesia (a response to painful stim...

Claims

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Application Information

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IPC IPC(8): A01N43/38
Inventor A·S·利帕P·斯科尔尼克A·巴齐尔陈正明J·W·埃普斯坦
Owner DOV PHARMA
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