Use of neurosteroids to treat neuropathic pain
Ganaxolone (3α-hydroxy-3β-methyl-5β-pregnan-20-one) and 3α-hydroxy-3β-methyl-5β-pregnan-20-one and their physiologically cleavable esters are useful for treating neuropathic pain. Compositions comprising a pharmaceutically acceptable excipient and an appropriate compound, along with methods for preparing the compositions are disclosed. Also disclosed are articles of manufacture wherein the composition is combine with labeling instructions for treating neuropathic pain.
1 . A method of treating neuropathic pain in a subject experiencing such pain by administering a therapeutically effective amount of a compound for a time sufficient to reduce the intensity of such pain in the subject, wherein the neurosteroid has the formula:
wherein
R 1 is methyl, R 2 is hydroxyl or a physiologically cleavable ester thereof, R 3 is hydrogen, R 4 is a hydrogen, and R 5 is acetyl (CH 3 C(O)—), and the pharmaceutically acceptable esters and salts of the hydroxyl group.
2 . The method of claim 1 , wherein R 2 is hydroxyl and R 4 is in the alpha configuration.
3 . The method of claim 1 , wherein R 2 is hydroxyl and R 4 is in the beta configuration.
4 . The method of claim 1 , wherein the compound is delivered to the subject at a rate of 0.1 mg/kg to 10 mg/kg body weight of the subject.
5 . The method of claim 1 wherein the compound is ganaxolone.
6 . The method of claim 1 wherein the compound is a physiologically cleavable ester of ganaxolone.
7 . A composition for treating neuropathic pain in a subject experiencing such pain which comprises a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of the formula:
wherein
R 1 is methyl, R 2 is hydroxyl or a physiologically cleavable ester thereof, R 3 is hydrogen, R 4 is a hydrogen, and R 5 is acetyl (CH 3 C(O)—)
8 . The composition of claim 7 , wherein R 2 is hydroxyl and R 4 is in the alpha configuration, i.e., ganaxolone.
9 . The composition of claim 7 , wherein R 2 is hydroxyl and R 4 is in the beta configuration.
10 . The composition of claim 7 , wherein the compound is about 1% to about 90% by weight of the composition.
11 . The composition of claim 7 wherein the compound is a physiologically cleavable ester of ganaxolone.
12 . An article of manufacture comprising:
(a) a composition comprising a pharmaceutically acceptable excipient and compound of the formula:
wherein
R 1 is methyl, R 2 is hydroxyl or a physiologically cleavable ester thereof, R 3 is hydrogen, R 4 is a hydrogen, and R 5 is acetyl (CH 3 C(O)—), and
(b) a label with instructions for using the composition to treat neuropathic pain in a patient.
13 . The article of claim 12 , wherein R 2 is hydroxyl and R 4 is in the alpha configuration, i.e., ganaxolone.
14 . The article of claim 12 , wherein R 2 is hydroxyl and R 4 is in the beta configuration.
15 . The article of claim 12 , wherein the label provides instructions to deliver the compound to the subject at a rate of 0.1 mg/kg to 10 mg/kg body weight of the subject.
16 . The method of claim 12 wherein the compound is a physiologically cleavable ester of ganaxolone.
17 . A method for preparing a pharmaceutical composition useful for treating neuropathic pain, which method comprises:
(a) combining a pharmaceutically acceptable excipient with a compound of the formula:
wherein
R 1 is methyl, R 2 is hydroxyl or a physiologically cleavable ester thereof, R 3 is hydrogen, R 4 is a hydrogen, and R 5 is acetyl (CH 3 C(O)—).
to form a formulation acceptable for administration to a human; and
(b) packaging the formulation with written instructions for the treatment of neuropathic pain by administering the formulation to a patient in need of therapy.
18 . The method of claim 17 , wherein R 2 is hydroxyl and R 4 is in the alpha configuration, i.e., ganaxolone.
19 . The method of claim 17 , wherein R 2 is hydroxyl and R 4 is in the beta configuration.
20 . The method of claim 17 , wherein the instructions indicate the compound is delivered to the subject at a rate of 0.1 mg/kg to 10 mg/kg body weight of the subject.
21 . The method of claim 17 wherein the compound is a physiologically cleavable ester of ganaxolone.