COMPOSITIONS AND METHODS FOR THE TREATMENT OF DISORDERS OF THE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS

• US 20090258844A1
• Filed: 04/15/2009
• Published: 10/15/2009
• Est. Priority Date: 12/23/1998
• Status: Abandoned Application

• Current Assignee: NeuroTherapeutics Pharma, Inc.
• Original Assignee: NeuroTherapeutics Pharma, Inc.
• Inventors: HOCHMAN, Daryl W.
• Application Number:
  US12/424,172
• Publication Number:
  US 20090258844A1
• Time in Patent Office: Days
• US Class Current: 514/162
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 31/635 having a heterocyclic ring, e.g. sulfadiazine
• 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

Abstract

The present invention relates to methods and compositions for treating selected conditions of the central and peripheral nervous systems employing non-synaptic mechanisms. More specifically, one aspect of the present invention relates to methods and materials for treating seizure and seizure disorders, epilepsy, status epilepticus, migraine, spreading depression, intracranial hypertension; for treating the pathophysiological effects of head trauma, stroke, ischemia and hypoxia; for treating or protecting from the pathophysiological effects of neurotoxic agents such as ethanol; and for treating neuropsychiatric disorders and central nervous system edema by administering agents that modulate ionic concentrations and/or ionic gradients in the brain, particularly ion-dependent or cation-chloride cotransporter antagonists. Electrolyte cotransport antagonists and combinations of such compositions with other agents for treating various conditions are disclosed.

Claims

1. A method for treating a condition in a mammalian subject in need thereof, comprising administering an effective amount of a treatment composition comprising at least one component selected from the group consisting of:

bumetanide and ethacrinic acid, wherein the condition is selected from the group consisting of;

seizures;

seizure disorders;

epilepsy; and

status.

2. The method of claim 1, wherein the treatment composition has cation-chloride cotransporter antagonist activity.

3. The method of claim 1, wherein the treatment composition further comprises a component selected from the group consisting of:

phenytoin;

carbamazepine;

barbiturates;

Phenobarbital;

pentobarbital;

mephobarbital;

trimethadione;

mephenytoin;

paramethadione;

phenthenylate;

phenacemide;

metharbital;

benzchlorpropamide;

phensuximide;

primidone;

methsuximide;

ethotoin;

aminoglutethimide;

diazepam;

clonazepam;

clorazepate;

fosphenytoin;

ethosuximide;

valporate;

felbamate;

gabapentin;

lamotrigine;

topiramate;

vigrabatrin;

tiagabine;

zonisamide;

clobazam;

thiopental;

midazoplam;

propofol;

levetiracetam;

oxcarbazepine;

CCPene;

GYK152466;

sumatriptan;

non-steroidal anti-inflammatory drugs;

neuroleptics;

corticosteroids;

vasoconstrictors;

beta-blockers;

antidepressants;

anticonvulsants;

Depakote;

Ergot alkaloids;

tryptans;

Acetaminophen;

caffeine;

Ibuprofen;

Proproxyphene;

oxycodone;

codeine;

isometheptene;

serotonin receptor agonists;

ergotamine;

dihydroergotamine;

sumatriptan;

propranolol;

metoprolol;

atenolol;

timolol;

nadolol;

nifeddipine;

nimodipine;

verapamil;

aspirin;

ketoprofen;

tofenamic acid;

mefenamic acid;

naproxen;

methysergide;

paracetamol;

clonidine;

lisuride;

iprazochrome;

butalbital;

benzodiazepines; and

divalproex sodium.

4. The method of claim 1, additionally comprising administering an effective amount of a blood brain barrier permeability enhancer.

5. The method of claim 1, additionally comprising administering a hyperosmotic agent.

6. The method of claim 1, wherein the treatment composition is administered by at least one of the following:

intracranial administration;

local intracerebral administration;

administration into the cerebral spinal fluid;

or administration in a sustained release formulation.

7. The method of claim 1, wherein the treatment composition is formulated to facilitate crossing of the blood brain barrier.

9. A method for treating a condition in a mammalian subject in need thereof, comprising administering an effective amount of a treatment composition comprising at least one component selected from the group consisting of:

thiazide and thiazide-like compositions, wherein the condition is selected from the group consisting of;

seizures;

seizure disorders;

epilepsy; and

status.

10. The method of claim 9, wherein the treatment composition has cation-chloride cotransporter antagonist activity.

11. The method of claim 9, wherein the treatment composition further comprises a component selected from the group consisting of:

phenytoin;

carbamazepine;

barbiturates;

Phenobarbital;

pentobarbital;

mephobarbital;

trimethadione;

mephenytoin;

paramethadione;

phenthenylate;

phenacemide;

metharbital;

benzchlorpropamide;

phensuximide;

primidone;

methsuximide;

ethotoin;

aminoglutethimide;

diazepam;

clonazepam;

clorazepate;

fosphenytoin;

ethosuximide;

valporate;

felbamate;

gabapentin;

lamotrigine;

topiramate;

vigrabatrin;

tiagabine;

zonisamide;

clobazam;

thiopental;

midazoplam;

propofol;

levetiracetam;

oxcarbazepine;

CCPene;

GYK152466;

sumatriptan;

non-steroidal anti-inflammatory drugs;

neuroleptics;

corticosteroids;

vasoconstrictors;

beta-blockers;

antidepressants;

anticonvulsants;

Depakote;

Ergot alkaloids;

tryptans;

Acetaminophen;

caffeine;

Ibuprofen;

Proproxyphene;

oxycodone;

codeine;

isometheptene;

serotonin receptor agonists;

ergotamine;

dihydroergotamine;

sumatriptan;

propranolol;

metoprolol;

atenolol;

timolol;

nadolol;

nifeddipine;

nimodipine;

verapamil;

aspirin;

ketoprofen;

tofenamic acid;

mefenamic acid;

naproxen;

methysergide;

paracetamol;

clonidine;

lisuride;

iprazochrome;

butalbital;

benzodiazepines; and

divalproex sodium.

12. The method of claim 9, additionally comprising administering an effective amount of a blood brain barrier permeability enhancer.

13. The method of claim 9, additionally comprising administering a hyperosmotic agent.

14. The method of claim 9, wherein the treatment composition is administered by at least one of the following:

intracranial administration;

local intracerebral administration;

administration into the cerebral spinal fluid;

or administration in a sustained release formulation.

15. The method of claim 9, wherein the treatment composition is formulated to facilitate crossing of the blood brain barrier.