Methods of increasing tonic inhibition and treating secondary insomnia

Abstract

Methods of increasing tonic inhibition in a subject in need thereof, for example a subject with Fragile X syndrome or Angelman syndrome are disclosed. Methods of treating secondary insomnia in a subject with a neurodegenerative disease or disorder are also disclosed. The methods can include administering the subject an effective amount of 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) or a derivative thereof, or a pharmaceutically acceptable salt thereof, increase tonic inhibition in neurons of the subject; to increase slow wave sleep (SWS) and/or slow wave activity (SWA), normalize sleep architecture, reduce secondary insomnia, increase non-rapid eye movement (NREM) sleep, increase sleep continuity, enhance delta activity within NREM, increase or improve total sleep time (TST), increase or improve sleep efficiency, reduce total time awake (TAA), reduce number of awakenings (NWA), reduce latency to persistent sleep (LPS), or to reduce wake after sleep onset (WASO), in the subject, or any combination thereof.

What is claimed is: 
     
         1 . A method of treating Dementia with Lewy Bodies comprising administering to a patient in need thereof gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A method of treating Dementia with Lewy Bodies comprising administering to a patient in need thereof gaboxadol or a pharmaceutically acceptable salt thereof and a compound selected from the group consisting of memantine, galantamine, donepezil and rivastigmine. 
     
     
         3 . The method of  claim 2 , wherein memantine or a pharmaceutically acceptable salt thereof is administered at a dosage of between about 1 mg to about 30 mg. 
     
     
         4 . The method of  claim 2 , wherein memantine or a pharmaceutically acceptable salt thereof is administered at a dosage of about 5 mg or 10 mg. 
     
     
         5 . The method of  claim 2 , wherein memantine or a pharmaceutically acceptable salt thereof is administered at a dosage of about 7 mg, 14 mg, 21 mg, or 28 mg in a conventional release dosage form or an extended release dosage form. 
     
     
         6 . The method of  claim 1 , wherein the patient is administered 0.1 mg to 50 mg gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 1 , wherein the patient is administered 2.5 mg to 30 mg gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 1 , wherein the patient is administered a dose of gaboxadol or a pharmaceutically acceptable salt thereof ranging from 0.1 mg/kg to 3.0 mg/kg. 
     
     
         9 . The method of  claim 2 , wherein the patient is administered 1.0 mg to 30 mg galantamine or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 2 , wherein the patient is administered extended release galantamine or a pharmaceutically acceptable salt thereof at a dosage of 8 mg, 16 mg, or 24 mg. 
     
     
         11 . The method of  claim 2 , wherein the patient is administered 1.0 mg to 30 mg donepezil or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 2 , wherein the patient is administered donepezil or a pharmaceutically acceptable salt thereof at a dosage of 5 mg, 10 mg, or 23 mg. 
     
     
         13 . The method of  claim 2 , wherein the patient is administered 1.0 mg to 20 mg rivastigmine or a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 2 , wherein the patient is administered rivastigmine or a pharmaceutically acceptable salt thereof at a dosage of 4.6 mg, 9.5 mg, or 13.3 mg. 
     
     
         15 . The method of  claim 2 , wherein the patient is administered an oral solution of rivastigmine or a pharmaceutically acceptable salt thereof at a dosage of 1 mg/ml. 
     
     
         16 . The method of  claim 1 , wherein the patient is administered a subtherapeutic dosage of memantine or a pharmaceutically acceptable salt thereof, galantamine or a pharmaceutically acceptable salt thereof, donepezil or a pharmaceutically acceptable salt thereof, or rivastigmine or a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 1 , wherein the patient is administered about 1 mg to about 20 mg gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 1 , wherein the patient is administered about 1 mg to about 15 mg gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 1 , wherein the patient is administered about 1 mg to about 10 mg gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         20 . The method of  claim 1 , wherein the patient is administered about 5 mg or about 10 mg gaboxadol or a pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 1 , further comprising administering memantine or a pharmaceutically acceptable salt thereof.