Vasoconstrictor cannabinoid analogs
Methods and compounds for reversing pathological vasodilation of blood vessels, for example vasodilation caused by activation of CB1-like receptors, by administering to a subject a therapeutically effective amount of a compound sufficient to induce vasoconstriction, the compound comprising: wherein dashed lines independently represent either a single or a double bond, R 1 is a lower alkyl, R 2 is a lower alkyl, R 3 is a lower alkyl or halogen, R 4 is a lower alkyl or hydrogen, R 5 is a lower alkyl or hydrogen, R 6 is a hydrogen, lower alkyl or halogen, and R 7 is a hydrogen, lower alkyl or halogen. The vasoconstrictor can be used for a variety of purposes, including hemostasis or the treatment of shock, for example vasodilatory shock syndromes such as septic shock.
1. A compound having the chemical structure:
wherein dashed lines independently represent either a single or a double bond;
R 1 is a lower alkyl;
R 2 is a lower alkyl;
R 3 is halogen or a lower alkyl having 1 to 3 carbons;
R 4 is a lower alkyl or hydrogen;
R 5 is a lower alkyl or hydrogen;
R 6 is a hydrogen, lower alkyl or halogen;
R 7 is a hydrogen, lower alkyl or halogen, and
wherein the compound is an enantiomerically pure (−) stereoisomer.
2. A compound having the chemical structure
wherein dashed lines independently represent either a single or a double bond;
R 1 is a lower alkyl;
R 2 is a lower alkyl;
R 3 is a halogen or a lower alkyl having 1 to 3 carbons;
R 4 is a lower alkyl or hydrogen;
R 5 is a lower alkyl or hydrogen, and
wherein the compound is an enantiomerically pure (−) stereoisomer.
3. A compound having the chemical structure
wherein R 1 is a lower alkyl;
R 2 is a lower alkyl;
R 3 is a halogen or lower alkyl having 1 to 3 carbons, and
wherein the compound is an enantiomerically pure (−) stereoisomer.
4. The compound of claim 3 , wherein R 3 is a methyl and the compound comprises:
5. The compound of claim 3 , wherein
R 1 is a methyl or propyl;
R 2 is a methyl or propyl; and
R 3 is a methyl.
6. The compound of claim 3 , wherein said compound has the chemical structure
7. A method of vasoconstricting blood vessels by selectively antagonizing the CB1-like receptor, comprising administering to a subject a therapeutically effective amount of a compound sufficient to induce vasoconstriction, the compound comprising:
wherein dashed lines independently represent either a single or a double bond;
R 1 is a lower alkyl;
R 2 is a lower alkyl;
R 3 is a lower alkyl or halogen;
R 4 is a lower alkyl or hydrogen;
R 5 is a lower alkyl or hydrogen;
R 6 is a hydrogen, lower alkyl or halogen;
R 7 is a hydrogen, lower alkyl or halogen, and
thereby selectively antagonizing the CB1-like receptor.
8. The method of claim 7 , wherein the compound comprises:
wherein dashed lines independently represent either a single or a double bond;
R 1 is a lower alkyl;
R 2 is a lower alkyl;
R 3 is a halogen or a lower alkyl;
R 4 is a lower alkyl or hydrogen; and
R 5 is a lower alkyl or hydrogen.
9. The method of claim 8 , wherein the compound comprises:
wherein R 1 is a lower alkyl;
R 2 is a lower alkyl; and
R 3 is a halogen or lower alkyl.
10. The method of claim 9 , wherein the compound comprises:
11. The method of claim 7 , wherein the method comprises administering the compound to a subject experiencing or at risk of experiencing shock.
12. The method of claim 8 , wherein the method comprises administering the compound to a subject experiencing or at risk of experiencing vasodilatory shock.
13. The method of claim 12 , wherein the method comprises administering the compound to a subject experiencing or at risk of experiencing septic shock.
14. The method of claim 7 , wherein the method is a method of vasoconstricting blood vessels that are dilated by the activation of a CB1-like receptor.
15. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 .
16. The pharmaceutical composition of claim 15 , comprising an enantiomerically pure (−) stereoisomer of a compound having the chemical structure
17. A kit for vasoconstricting blood vessels in a subject comprising a container comprising the compound of claim 1 .
18. The kit of claim 17 , further comprising a container comprising another vasoconstrictive, inotropic, or antibiotic agent.
19. The kit of claim 18 , wherein the vasoconstrictive or inotropic agent is norepinephrine, dopamine, or dobutamine.
20. The kit of claim 17 , further comprising instructions for administering the compound to a subject.
21. The method of claim 7 , wherein the compound is an enantiomerically pure (−) stereoisomer.
22. The method of claim 7 , wherein the compound is a substantially pure antagonist of the CB1-like receptor.
23. The method of claim 7 , wherein the compound does not block the CB1 receptor.
24. A selective and substantially pure antagonist of the CB1-like receptor, comprising an enantiomerically pure (−) stereoisomer having the chemical structure: