Compositions and methods relating to solenopsins and their uses in treating neurological disorders and enhancing physical performance

• US 9,943,554 B2
• Filed: 01/25/2016
• Issued: 04/17/2018
• Est. Priority Date: 07/10/2006
• Status: Active Grant

• Current Assignee: Synapsin Pharmaceuticals Inc.
• Original Assignee: Synapsin Pharmaceuticals Inc.
• Inventors: Dorsey, Denis, Kindy, Mark S.
• Primary Examiner(s): Hui, San Ming R
• Application Number:
  US15/005,440
• Publication Number:
  US 20160317588A1
• Time in Patent Office: 813 Days
• Field of Search: 514315
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 35/63 Arthropods aquatic crustaceans A61K35/612
• CPC Class Codes: A61K 35/64 Insects, e.g. bees, wasps or fleas
• CPC Class Codes: C07D 211/12 with only hydrogen atoms attached to the ring nitrogen atom

Abstract

Provided herein are piperidine alkaloids and uses thereof in neurological disorders and physical enhancement applications.

Claims

1. A method of treating a human subject diagnosed with neurodegenerative disease, comprising administering to the subject a therapeutically effective amount of a composition comprising a piperidine alkaloid, wherein the piperidine alkaloid comprises the formula:

2. The method of claim 1, wherein the composition comprises an extract of fire ant (Solenopsis invicta) venom.

3. The method of claim 1, wherein the composition further comprises a second piperidine alkaloid that comprises the formula:

4. The method of claim 1, wherein the piperidine alkaloid is selected from the group consisting of cis-2-methyl-6-undecylpiperidine, cis-2-methyl-6-tridecylpiperidine, cis-2-methyl-6-pentadecylpiperidine, cis-2-methyl-6-(cis-4-tridecen-1-yl)piperidine, and cis-2-methyl-6-(cis-4-pentadecen-1-yl)piperidine.

5. The method of claim 1, wherein the piperidine alkaloid is 2-methyl-6-undecylpiperidine.

6. The method of claim 1, wherein the subject has been diagnosed with Alzheimer'"'"'s disease.

7. The method of claim 1, wherein the composition is administered to the subject orally, systemically, or intracranially.

9. The method of claim 1, wherein the composition further comprises a pharmaceutically acceptable carrier, excipient, or additive.

10. The method of claim 1, wherein the composition further comprises an antimicrobial agent, an anti-inflammatory agent, an anesthetic, or combinations thereof.

11. The method of claim 1, further comprising administering to the subject at least one of an opioid, opioid peptides, morphine, hydroxymorphine, fentanyl, oxycodone, codeine, capsaicin, carbamazepine, primidone, gabapentin, pregabalin, diazepam, felbamate, fluorofelbamate, lamotrigine, lacosamide, levetiracetam, phenobarbital, phenyloin, fos-phenyloin, topiramate, valproate, vigabatrin, zonisamide, oxcarbazepine, nonsteroidal anti-inflammatory drugs, local anesthetics, glutamate receptor antagonists, NMDA antagonists, alpha-adrenoceptor agonists, alpha-adrenoceptor agonists antagonists, adenosine, cannabinoids, NK-1 antagonist (CI-1021), antidepressants, analogs of galanin, derivatives of galanin, somatostatin, delta-sleep inducing peptide, enkephalins, oxytocin, cholecystikinin, calcitonin, cortistatin, nociceptin, neuropeptide-based therapeutics, or pluronic P85 block copolymer, or combinations thereof.

12. The method of claim 1, wherein R¹ is a C11 alkyl group.

13. The method of claim 12, wherein the piperidine alkaloid is selected from the group consisting of cis-2-methyl-6-undecylpiperidine, cis-2-methyl-6-tridecylpiperidine, cis-2-methyl-6-pentadecylpiperidine, cis-2-methyl-6-(cis-4-tridecen-1-yl)piperidine, and cis-2-methyl-6-(cis-4-pentadecen-1-yl)piperidine.

8. A method of treating a subject diagnosed with Alzheimer'"'"'s disease, comprising administering to the subject a composition comprising a piperidine alkaloid, wherein the piperidine alkaloid comprises the formula:

14. The method of claim 8, wherein the composition comprises an extract of fire ant (Solenopsis invicta) venom.

15. The method of claim 8, wherein the composition further comprises a second piperidine alkaloid that comprises the formula:

16. The method of claim 8, wherein the piperidine alkaloid is selected from the group consisting of cis-2-methyl-6-undecylpiperidine, cis-2-methyl-6-tridecylpiperidine, cis-2-methyl-6-pentadecylpiperidine, cis-2-methyl-6-(cis-4-tridecen-1-yl)piperidine, and cis-2-methyl-6-(cis-4-pentadecen-1-yl)piperidine.