Cardioprotective delta opioid receptor agonists and methods of using same

• US 7,314,880 B2
• Filed: 12/31/2003
• Issued: 01/01/2008
• Est. Priority Date: 01/02/2003
• Status: Expired due to Fees

• Current Assignee: DMK Pharmaceuticals Corporation, Enta Holding LLC
• Original Assignee: Mount Cook Biosciences, Inc.
• Inventors: Gengo, Peter J., Ma, Xin, Pendergast, William, Chang, Kwen-Jen
• Primary Examiner(s): KWON, YONG SOK
• Application Number:
  US10/749,437
• Publication Number:
  US 20040171622A1
• Time in Patent Office: 1,462 Days
• Field of Search: 514/266.4, 514/255.4, 514/253.01, 514/282, 514/252.13
• US Class Current: 514/255.04
• 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 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/50 Pyridazines; Hydrogenated pyridazines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to compositions and methods of treatment for cardioprotection through the use of non-peptidic delta opioid receptor agonist compound(s) that mediate cardioprotective effects of ischemic preconditioning. The compounds are used to reduce injury associated with ischemia and reperfusion of cardiac tissue. Further, the compounds may be used in solutions preserving the viability of an isolated organ.

Claims

1. A method of reducing ischemic damage in cardiac tissue in a subject comprising:

administering to the subject in need thereof an effective amount of a composition comprising a non-analgesic diarylmethylpiperazine compound of the general formula;

2. A method of reducing ischemic damage in cardiac tissue in a subject comprising:

administering to the subject in need thereof an effective amount of a therapeutic composition comprising a non-analgesic diarylmethylpiperazine compound of the formula;

3. A method of reducing ischemic damage in cardiac tissue in a mammal, the method comprising:

administering to the mammal in need thereof an effective amount of a non-analgesic diarylmethylpiperazine compound of the formula;

4. The method according to claim 3, wherein the diarylmethylpiperazine compound is administered multiple times concurrently with the onset of an ischemic event.

5. The method according to claim 3, wherein the diarylmethylpiperazine compound is administered to the mammal to reduce cardiac tissue damage in an individual in a symptomatic phase of ischemic heart disease.

6. The method according to claim 3, wherein the diarylmethylpiperazine compound is administered after the onset of an ischemic event.

7. The method according to claim 3, further comprising administering a second compound that effectuates a corrective cardiac response.

8. The method according to claim 7, wherein the second compound is selected from the group consisting of nitrates, beta-adrenergic blockers, calcium channel antagonists, ACE inhibitors, non-peptide angiotensin II antagonists, IIb/IIIa antagonists and aspirin.

9. The method according to claim 7, wherein the second compound is administered contemporaneously with the diarylmethylpiperazine compound.

10. The method according to claim 3, wherein the diarylmethylpiperazine compound is administered by a mode of administration selected from the group consisting of parenteral, non-parenteral, oral, rectal, topical, nasal, ophthalmic, subcutaneous, intramuscular, intravenous, transdermal, spinal, intrathecal, intra-articular, intra-arterial, sub-arachnoid, sublingual, oral mucosal, bronchial, lymphatic, and intra-uterine administration.

11. The method according to claim 3, wherein the mammal is a human.

12. A method of treating ischemia and reperfusion injury in cardiac tissue in a mammal comprising administering to the mammal in need thereof an effective amount of a non-analgesic delta opioid receptor agonist of the formula:

13. The method of claim 12, wherein the second compound is arginine hydrochloride.

14. A method of effectuating ischemic preconditioning of cardiac tissue in a subject in need thereof, the method comprising:

administering to the subject an effective amount of a non-analgesic diarylmethylpiperazine compound of the formula;

15. The method of claim 14, wherein the compound is administered by a mode of administration selected from the group consisting of parenteral, non-parenteral, oral, rectal, topical, nasal, ophthalmic, subcutaneous, intramuscular, intravenous, transdermal, spinal, intrathecal, intra-articular, intra-arterial, sub-arachnoid, sublingual, oral mucosal, bronchial, lymphatic, and intra-uterine administration.

16. The method according to claim 14, further comprising administering a second compound that effectuates a corrective cardiac response.

17. The method according to claim 16, wherein the second compound is selected from the group consisting of nitrates, beta-adrenergic blockers, calcium channel antagonists, ACE inhibitors, non-peptide angiotensin II antagonists, IIb/IIIa antagonists and aspirin.

18. The method according to claim 16, wherein the second compound is administered contemporaneously with the diarylmethylpiperazine compound.