Methods for treating hypersomnia

Abstract

Provided herein are methods, formulations and dosing regimens for treating hypersomnia in a subject. For instance, methods provided herein comprise administering a GABA A chloride channel blocker. In certain embodiments, the GABA A chloride channel blocker is pentylenetetrazol (PTZ).

1 . A method for treating narcolepsy in a subject comprising administering pentylenetetrazol (PTZ) to the subject having narcolepsy, wherein the administering is effective to treat the narcolepsy. 
     
     
         2 . The method of  claim 1 , wherein the PTZ is administered at least once daily for at least five consecutive days. 
     
     
         3 . The method of  claim 1 , wherein the PTZ antagonist is administered, twice a day. 
     
     
         4 . The method of  claim 1 , wherein the PTZ is administered at a dose of about 1 mg to 1,500 mg. 
     
     
         5 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the PTZ is administered at a dose of about 25 mg to 600 mg. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the PTZ is administered at a dose sufficient to achieve a mean Cmax of about 50 to 20,000 ng/ml. 
     
     
         10 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the PTZ is administered at a dose sufficient to achieve a mean Cmax of about 3,000 to 6,000 ng/ml. 
     
     
         14 . The method of  claim 1 , wherein the PTZ is administered prior to or during the subject's night-time sleep. 
     
     
         15 . The method of  claim 1 , wherein the PTZ is administered prior to or during the subject's morning wake-up period. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the PTZ is administered in an oral formulation. 
     
     
         18 . The method of  claim 1 , wherein the PTZ is administered in a delayed release formulation. 
     
     
         19 . The method of  claim 18 , wherein the delayed release formulation delays the peak concentration of PTZ in brain by 30 minutes to 12 hours from the time of administration. 
     
     
         20 . The method of  claim 18 , wherein the delayed release formulation releases PTZ during the subject's night-time sleep or morning wake-up period. 
     
     
         21 . The method of  claim 1 , wherein the PTZ is administered in a sustained release formulation. 
     
     
         22 . The method of  claim 21 , wherein the sustained release formulation maintains a therapeutically effective dose of the PTZ for 30 minutes to 12 hours after administration. 
     
     
         23 - 27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the subject is human. 
     
     
         29 - 33 . (canceled) 
     
     
         34 . The method of  claim 1 , wherein the narcolepsy is narcolepsy without cataplexy. 
     
     
         35 . The method of  claim 1 , wherein the narcolepsy is narcolepsy with cataplexy (narcolepsy Type I). 
     
     
         36 . The method of  claim 1 , wherein the subject having narcolepsy is assessed according to the Stanford Sleepiness Scale (SSS), the Epworth Sleepiness Scale (ESS), the multiple sleep latency (MSL) test, the maintenance of wakefulness (MWT) test, objective psychomotor vigilance (PVT) tasks, the Functional Outcomes of Sleep Questionnaire (FOSQ), the Multidimensional Fatigue Inventory (MFI), the Clinical Global Impression of Severity (CGI-S), the Clinical Global Impression of Change (CGI-C), the Beck Depression Inventory (BDI-II), self-reported fogginess scores, self-reported mood scores or self-reported sleepiness scores. 
     
     
         37 . The method of  claim 35 , wherein the subject having narcolepsy improves by at least about 3 points on the ESS, at least about 2 min for sleep onset latency (SOL) on MWT, at least about 8 points on the FOSQ, at least about 4 points on one or more MFI scales, at least one point on CGI-S or CGI-C, at least about 4 points on the BDI-II, or at least about 1.0 point on a self-reported fogginess score. 
     
     
         38 . The method of  claim 1 , wherein PTZ is administered twice daily at dose of 100 mg for a period of at least one week.