USE OF CIS-EPOXYEICOSATRIENOIC ACIDS AND INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE TO TREAT CONDITIONS MEDIATED BY PBR, CB2, and NK2 RECEPTORS

Abstract

The invention relates to the discovery that cis-epoxyeicosatraenoic acids (EETs) bind to and act as agonists of peripheral benzodiazepine receptor and the cannabinoid CB 2 receptor. The invention provides methods of reducing symptoms of conditions whose activity is mediated by these receptors, including inhibiting anxiety, inhibiting the growth of cancer cells expressing peripheral benzodiazepine receptors, and reducing oxygen radical damage to cells, by contacting the cells with a cis-epoxyeicosantrienoic acid, an inhibitor of soluble epoxide hydrolase (sEH), or both. The invention further provides methods of inhibiting irritable bowel syndrome by administering to individuals with inhibiting irritable bowel syndrome a cis-epoxyeicosantrienoic acid, an inhibitor of soluble epoxide hydrolase (sEH), or both. In some embodiments, the method comprises administering to the individual a nucleic acid which inhibits expression of sEH.

1 . A method of relieving a condition selected from the group consisting of anxiety, panic attacks, agitation, status epilepticus, other forms of epilepsy, symptoms of alcohol or opiate withdrawal, insomnia, or mania in a subject in need thereof, said method comprising administering to said subject an effective amount of an agent or agents selected from the group consisting of a cis-epoxyeicosantrienoic acid (“EET”), an inhibitor of soluble epoxide hydrolase (“sEH”), and a combination of an EET and an inhibitor of sEH, thereby relieving said condition in said subject. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . A method of  claim 1 , wherein the agent is an inhibitor of sEH. 
     
     
         5 . A method of  claim 1 , wherein said condition is anxiety. 
     
     
         6 . A method of inhibiting growth of cancer cells expressing peripheral benzodiazepine receptors (PBR) or CB2 receptors, said method comprising contacting said cells with an effective amount of an agent or agents selected from the group consisting of a cis-epoxyeicosantrienoic acid (“EET”), an inhibitor of soluble epoxide hydrolase (“sEH”), and a combination of an EET and an inhibitor of sEH, thereby inhibiting the growth of said cancer cells. 
     
     
         7 . A method of  claim 6 , wherein the cancer cells are glioma cells. 
     
     
         8 . A method of  claim 6 , wherein the cells are astrocytoma cells. 
     
     
         9 . A method of  claim 6 , wherein the cells are breast cancer cells. 
     
     
         10 . A method of  claim 6 , wherein the agent is an EET. 
     
     
         11 . A method of  claim 6 , wherein the EET is selected from the group consisting of 14,15-EET, and 11,12-EET. 
     
     
         12 . A method of  claim 6 , wherein the agent is an inhibitor of sEH. 
     
     
         13 . A method of  claim 6 , wherein EET or said inhibitor of sEH, or both, are contained in a material which releases said EET or said inhibitor, or both, over time. 
     
     
         14 . A method of reducing oxygen radical damage to cells, said method comprising contacting said cells with an effective amount of an agent or agents selected from the group consisting of a cis-epoxyeicosantrienoic acid (“EET”), an inhibitor of soluble epoxide hydrolase (“sEH”), and a combination of an EET and an inhibitor of sEH, thereby reducing oxygen radical damage to said cells. 
     
     
         15 . A method of  claim 14 , wherein the agent is an EET. 
     
     
         16 . A method of  claim 14 , wherein the EET is selected from the group consisting of 14,15-EET, 8,9-EET and 11,12-EET. 
     
     
         17 . A method of  claim 14 , wherein the agent is an inhibitor of sEH. 
     
     
         18 . A method of  claim 14 , wherein EET or said inhibitor of sEH, or both, are administered by applying to the skin a topical formulation comprising said EET or said inhibitor of sEH or both. 
     
     
         19 . A method of  claim 18 , wherein said topical formulation further comprises a sunscreen or sunblock. 
     
     
         20 . A method of relieving irritable bowel syndrome (IBS) in a subject in need thereof, said method comprising administering to said subject an effective amount of an agent or agents selected from the group consisting of a cis-epoxyeicosantrienoic acid (“EET”), an inhibitor of soluble epoxide hydrolase (“sEH”), and a combination of an EET and an inhibitor of sEH, thereby relieving IBS in said subject. 
     
     
         21 - 22 . (canceled) 
     
     
         23 . A method of  claim 20 , wherein the agent is an inhibitor of sEH.