Cyclic glycyl-2-allyl proline improves cognitive performance in impaired animals
Embodiments of this invention provide methods for therapeutic use of cyclic G-2-Allyl Proline to treat cognitive disorders as well as manufacture of medicaments including tablets, capsules, injectable solutions that are useful for treatment of such conditions.
1. A method for relieving or alleviating of cognitive impairment caused by a disease, injury, or condition in a mammal in need thereof, comprising: administering a pharmaceutically effective amount of cyclic Glycyl-2-Allyl Proline (cG-2-AllyIP) to said mammal, where said disease is selected from the group consisting of Alzheimer's disease, Huntington's disease, Lewy Body disease, Dementia, and multi-infarct dementia, said injury is selected from the group consisting of neurotoxic injury, cerebral hypoxia/ischemia, traumatic brain injury, coronary artery bypass surgery, where said condition is normal aging, age-related memory loss, memory impairment, cholinergic hypofunction, vascular narrowing or blockage in the brain, neuroinflammation, mild cognitive impairment, cerebral atrophy, frontotemporal lobar degeneration, Pick's disease, HIV infection, Down's syndrome, and loss of synaptic plasticity.
2. The method of claim 1 , wherein said cG-2-AllyIP comprises an aqueous solution and one or more pharmaceutically acceptable excipients, additives, carriers or adjuvants.
3. The method of claim 1 , wherein said cG-2-AllyIP further comprises one or more excipients, carriers, additives, adjuvants or binders in a tablet or capsule.
4. The method of claim 1 , wherein said disorder is a mild cognitive impairment or a dementia.
5. The method of claim 1 , wherein said cyclic G-2-AllyIP is administered via an oral, intraperitoneal, intravascular, peripheral circulation, subcutaneous, intraorbital, ophthalmic, intraspinal, intracisternal, topical, infusion, implant, aerosol, inhalation, scarification, intracapsular, intramuscular, intranasal, buccal, transdermal, pulmonary, rectal, or vaginal route.
6. The method of claim 1 , wherein said effective amount has a lower limit of about 0.001 milligrams per kilogram mass (mg/kg) of the animal and an upper limit of about 100 mg/kg.
7. The method of claim 1 , wherein said cognitive impairment is caused by cholinergic hypofunction.
8. The method of claim 1 , wherein said cognitive impairment is age-related memory loss.
9. The method of claim 7 , wherein said cholinergic hypofunction is caused by scopalamine.
10. The method of claim 1 , wherein said cognitive impairment is caused by a decrease in glutamate receptors in the granular cell layer (CA1) of the hippocampus of said mammal.
11. The method of claim 1 , wherein said cG-2-AllylP causes an increase in AMPA receptors in the granular cell layer (CA1) of the hippocampus of said mammal.
12. The method of claim 1 , wherein said cG-2-AllylP causes an increase in neuronal plasticity caused by said cG-2-AllylP in the granule cell layer (CA1) and the pyramidal cell layer (CA3) regions of said mammal's hippocampus.
13. The method of claim 1 , wherein said cG-2-AllylP causes an increase in spatial memory in said mammal.
14. The method of claim 1 , wherein said cG-2-AllylP causes in increase in novelty recognition in said mammal.
15. The method of claim 1 , wherein said cG-2-AllylP improves glutaminergic neurotransmission in the hippocampus of said mammal.
16. The method of claim 1 , wherein said cG-2-AllylP causes an increase in the number of pre-synaptic vesicles in the CA1 and C3 regions of said mammal's hippocampus.
17. The method of claim 1 , wherein said cG-2-AllylP causes an increase in synaptic density in the hippocampus of said mammal.
18. The method of claim 1 , said cerebral hypoxia/ischemia caused by traumatic brain injury.
19. The method of claim 1 , said cognitive impairment caused by multi-infarct dementia.
20. The method of claim 1 , said cognitive impairment caused by coronary arterial bypass surgery (CABG).
21. The method of claim 1 , said cognitive impairment caused by decreased cerebral perfusion.
22. The method of claim 1 , said cognitive impairment caused by normal aging.