Methods and pharmaceutical compositions for treating the animal central nervous system for psychiatric disorders

• US 8,592,485 B2
• Filed: 06/16/2011
• Issued: 11/26/2013
• Est. Priority Date: 06/17/2010
• Status: Active Grant

• Current Assignee: Healthpartners Research Foundation (Health Partners Institute For Education & Research)
• Original Assignee: Healthpartners Research Foundation (Health Partners Institute For Education & Research)
• Inventors: Bresin Hanson, Leah Ranae, Frey, William H. II
• Primary Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US13/161,934
• Publication Number:
  US 20110311654A1
• Time in Patent Office: 894 Days
• Field of Search: 514/616, 514/645
• US Class Current: 514/616
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 25/24 Antidepressants
• CPC Class Codes: C07C 259/06 having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms

Abstract

The present invention comprises methods and pharmaceutical compositions for intranasal delivery of effective amounts of DFO directly to the CNS, in particular the brain treatments that inhibit GSK3b in patients with psychiatric disorders including, but not limited to, bipolar disorder, depression, ADHD and schizophrenia. In addition a treatment composition is disclosed which comprises DFO and in certain embodiments combines DFO with one or more of the psychotropic drug types, i.e., antipsychotics, mood stabilizers and antidepressants. Moreover, a treatment for treating impairment of neural plasticity through inhibition of GSK3b is provided as well as prevention of apoptosis of cells through inhibition of GSK3b.

Claims

1. A method to treat patients with bipolar disorder, depression, ADHD, or schizophrenia comprising:

administering at least one effective dose of deferoxamine (DFO) to the upper one-third of the patient'"'"'s nasal cavity;

inhibiting GSK-3b in the patient'"'"'s brain; and

treating the patient with bipolar disorder, depression, ADHD, or schizophrenia.

2. The method of claim 1, wherein the inhibiting of GSK-3b in the patient'"'"'s brain results from phosphorylation of the GSK-3b.

3. The method of claim 2, wherein the at least one effective dose is within the range of 0.0001-1.0 mg/kg and which provides a brain concentration within the range of 0.1 nM-50 μ

M.

4. The method of claim 1, further comprising administering an effective dose of the group consisting of a mood stabilizer, an antidepressant and an antipsychotic agent.

5. A method for protecting central nervous system cells from GSK-3-promoted apoptosis, comprising:

administering at least one effective dose of deferoxamine (DFO) to the upper one-third of the patient'"'"'s nasal cavity;

inhibiting GSK-3b in the patient'"'"'s brain; and

protecting central nervous system cells from GSK-3-promoted apoptosis.

6. The method of claim 5, wherein the inhibiting of GSK-3b in the patient'"'"'s brain results from phosphorylation of the GSK-3b.

7. The method of claim 6, wherein the at least one effective dose is within the range of 0.0001-1.0 mg/kg and which provides a brain concentration within the range of 0.1 nM-50 μ

M.

8. A method for treating central nervous system cells of impairment of neural plasticity caused by GSK-3, comprising:

administering at least one effective dose of deferoxamine (DFO) to the upper one-third of the patient'"'"'s nasal cavity;

inhibiting GSK-3b in the patient'"'"'s brain; and

treating the central nervous system cells for impairment of neural plasticity caused by GSK-3.

9. The method of claim 8 wherein the inhibiting of GSK-3b in the patient'"'"'s brain results from phosphorylation of the GSK-3b.

10. The method of claim 8, wherein the at least one effective dose is within the range of 0.0001-1.0 mg/kg and which provides a brain concentration within the range of 0.1 nM-50 μ

M.