Preventing neuronal degeneration in Alzheimer's disease

• US 5,877,173 A
• Filed: 08/28/1996
• Issued: 03/02/1999
• Est. Priority Date: 08/28/1996
• Status: Expired due to Fees

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Olney, John W., Farber, Nuri B.
• Primary Examiner(s): Spivack, Phyllis G.
• Application Number:
  US08/704,093
• Time in Patent Office: 916 Days
• Field of Search: 514/220, 514/217
• US Class Current: 514/217
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Abstract

A method for reducing progressive neuronal degeneration due to Alzheimer'"'"'s disease is disclosed wherein a neuroprotective drug selected from the group consisting of clozapine, olanzapine and fluperlapine, and salts, isomers and analogs thereof, is administered.

Claims

1. A method for reducing progressive neuronal degeneration due to Alzheimer'"'"'s disease, comprising the step of administering, to a human patient suffering from or at elevated risk of Alzheimer'"'"'s disease, a neuroprotective drug selected from the group consisting of clozapine, olanzapine, and fluperlapine, and salts, isomers, and analogs thereof which (i) penetrate mammalian blood brain barriers, and (ii) are effective in preventing dizocilpine maleate from causing vacuole formation in posterior cingulate-retrosplenial neurons when administered to laboratory animals, wherein the neuroprotective drug is administered chronically to the patient in a dosage which is therapeutically effective in retarding progressive neuronal degeneration due to Alzheimer'"'"'s disease in the patient'"'"'s brain, but which does not produce intolerable side effects.

2. The method of claim 1, wherein one or more additional neuroprotective drugs is optionally administered to the patient on a sequential basis.

3. The method of claim 1, wherein at least two different neuroprotective drugs are co-administered to the patient over a single span of time.

4. The method of claim 1, wherein the neuroprotective drug suppresses activation of at least one type of muscarinic acetylcholine receptors inside mammalian brains.

5. The method of claim 4, wherein the neuroprotective drug selectively suppresses activity involving at least one muscarinic receptor class selected from the group consisting of m1 and m3 receptor classes.

6. The method of claim 1, wherein the neuroprotective drug suppresses activation of at least one class of muscarinic acetylcholine receptors selected from the group consisting of ml and m3 receptors, and also interacts with at least one other class of neuronal receptors selected from the group consisting of dopamine receptors, serotonin receptors, and norepinephrine receptors.

7. A method for reducing progressive neuronal degeneration in a patient suffering from Alzheimer'"'"'s disease, comprising the step of chronically administering to the patient a neuroprotective drug selected from the group consisting of clozapine, olanzapine, and fluperlapine, and salts, isomers, and analogs thereof which penetrate mammalian blood brain barriers, wherein the neuroprotective drug is therapeutically effective in retarding progressive neuronal degeneration due to NMDA receptor hypofunction in the patient'"'"'s brain, and does not produce intolerable side effects.

8. The method of claim 7, wherein the neuroprotective drug suppresses activation at m3 muscarinic acetylcholine receptors inside mammalian brains.