Methods and compositions for the treatment of neuropsychiatric disorders

• US 8,008,283 B2
• Filed: 10/17/2005
• Issued: 08/30/2011
• Est. Priority Date: 12/23/1998
• Status: Active Grant

• Current Assignee: Neuropro Therapeutics, Inc.
• Original Assignee: NeuroTherapeutics Pharma, Inc.
• Inventors: Hochman, Daryl W., Partridge, John J.
• Primary Examiner(s): Sznaidman; Marcos L
• Application Number:
  US11/251,724
• Publication Number:
  US 20060089350A1
• Time in Patent Office: 2,143 Days
• Field of Search: 514/183, 564/84
• US Class Current: 514/183
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants

Abstract

The present invention relates to methods and compositions for treating neuropathic pain and neuropsychiatric disorders by administering agents that are effective in reducing the effective amount, inactivating, and/or inhibiting the activity of a Na⁺—K⁺-2Cl⁻ (NKCC) cotransporter. In certain embodiments, the Na⁺—K⁺-2Cl⁻ co-transporter is NKCC1.

Claims

1. A compound of formula I:

2. The compound of claim 1, selected from the group consisting of:

bumetanide dibenzylamide and bumetanide diethylamide, or a pharmaceutically acceptable salt or tautomer thereof.

3. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt or tautomer thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

4. A pharmaceutical composition comprising a compound of claim 2, or a pharmaceutically acceptable salt or tautomer thereof, and a pharmaceutically acceptable carrier, excipient or diluent.

5. A compound which is bumetanide benzyl ester, bumetanide morpholinoethyl ester;

bumetanide 3-(dimethylaminopropyl) ester;

bumetanide N,N-diethylglycolamide ester;

bumetanide dimethylglycolamide ester;

bumetanide pivaxetil ester;

bumetanide propaxetil ester, or pharmaceutically acceptable salts or tautomers thereof.