Anticonvulsant activity of steroids

Abstract

The present invention relates to methods of preventing, inhibiting, delaying, and/or mitigating seizures by administration of a steroid, e.g., a neurosteroid, e.g., allopregnanolone.

What is claimed is: 
     
         1 . A method of treating, reducing, and/or mitigating symptoms associated with and/or caused by traumatic brain injury, Alzheimer's disease, epilepsy, anxiety, fragile X syndrome, post-traumatic stress disorder, lysosomal storage disorders (Niemann-Pick type C disease), depression (including post-partum depression), premenstrual dysphoric disorder, alcohol craving, and smoking cessation in a subject in need thereof, comprising administration to the subject a steroid. 
     
     
         2 . A method of treating, reducing, and/or mitigating symptoms associated with and/or caused by epilepsy, in a subject in need thereof, comprising administration to the subject a steroid. 
     
     
         3 . A method of accelerating the termination or abortion of an impending seizure in a subject in need thereof, comprising administration to the subject a steroid. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the steroid is a neurosteroid. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the neurosteroid is selected from the group consisting of allopregnanolone, allotetrahydrodeoxycorticosterone, ganaxolone, alphaxolone, alphadolone, hydroxydione, minaxolone, and Althesin. 
     
     
         6 . The method of  claim 5 , wherein the neurosteroid is allopregnanolone. 
     
     
         7 . The method of any one of  claims 5  to  6 , wherein the steroid is formulated in a cyclodextrin. 
     
     
         8 . The method of any one of  claims 1  to  7 , wherein the steroid is formulated in hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta-cyclodextrin sodium salt, or a mixture thereof. 
     
     
         9 . The method of any one of  claims 1  to  8 , wherein the subject is experiencing aura. 
     
     
         10 . The method of any one of  claims 1  to  9 , wherein the subject has been warned of an impending seizure. 
     
     
         11 . The method of any one of  claims 1  to  10 , wherein the subject is experiencing a seizure. 
     
     
         12 . The method of any one of  claims 1  to  11 , wherein the subject has status epilepticus. 
     
     
         13 . The method of any one of  claims 1  to  11 , wherein the subject has myoclonic epilepsy. 
     
     
         14 . The method of any one of  claims 1  to  11 , wherein the subject suffers from seizure clusters. 
     
     
         15 . The method of any one of  claims 1  to  14 , wherein the seizure is a tonic seizure. 
     
     
         16 . The method of any one of  claims 1  to  14 , wherein the seizure is a clonic seizure. 
     
     
         17 . The method of any one of  claims 1  to  16 , wherein the subject is a human. 
     
     
         18 . The method of any one of  claims 1  to  17 , wherein the steroid is administered intramuscularly (i.m.), subcutaneously (s.c.) or intravenously (i.v.). 
     
     
         19 . The method of any one of  claims 1  to  18 , wherein the steroid is administered at a dose in the range of about 0.25 mg/kg to about 15 mg/kg. 
     
     
         20 . The method of any one of  claims 1  to  19 , comprising treating, reducing, and/or mitigating symptoms associated with and/or caused by epilepsy by intramuscularly (i.m.), subcutaneously (s.c.) or intravenously (i.v.) administering allopregnanolone formulated in a sulfobutylether-beta-cyclodextrin sodium salt. 
     
     
         21 . The method of any one of  claims 1  to  20 , wherein the epilepsy is status epilepticus. 
     
     
         22 . A composition comprising or consisting essentially of a steroid and a cyclodextrin. 
     
     
         23 . The composition of  claim 22 , wherein the steroid is a neurosteroid. 
     
     
         24 . The composition of  claim 23 , wherein the neurosteroid is selected from the group consisting of allopregnanolone, allotetrahydrodeoxycorticosterone, ganaxolone, alphaxolone, alphadolone, hydroxydione, minaxolone, and Althesin. 
     
     
         25 . The composition of any one of  claims 22  to  24 , wherein the steroid is allopregnanolone. 
     
     
         26 . The composition of any one of  claims 22  to  25 , wherein the cyclodextrin is hydroxypropyl-beta-cyclodextrin, sulfobutylether-beta-cyclodextrin sodium salt, or a mixture thereof. 
     
     
         27 . The composition of any one of  claims 22  to  26 , wherein the composition is formulated for intramuscular (i.m.), subcutaneous (s.c.) or intravenous (i.v.) administration. 
     
     
         28 . The composition of any one of  claims 22  to  27 , wherein the composition comprises allopregnanolone and sulfobutylether-beta-cyclodextrin sodium salt.