Antidepressants and their analogues as long-acting local anesthetics and analgesics

1. A compound of the formula:

wherein Y 1 —Y 2 is selected from CH 2 —CH 2 , CH═CH, and CH 2 —O;

γ-β is selected from C═CH, CH—CH 2 , and N—CH 2 ;

each R′ and each R″ are independently selected from H and (C 1 -C 8 ) alkyl;

m is an integer ranging from 0 to 7;

each n is an integer ranging from 0 to m;

R 4 is selected from unsubstituted or substituted (C 1 -C 12 ) alkyl, (C 1 -C 12 ) alkenyl, (C 1 -C 12 ) alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl, heteroaryl, alkylheteroaryl, alkenylheteroaryl, alkynylheteroaryl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, polycycloalkyl, polycycloalkenyl, ketyl, and nothing;

R 5 is selected from unsubstituted or substituted (C 1 -C 12 ) alkyl, (C 1 -C 12 ) alkenyl, (C 1 -C 12 ) alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl, heteroaryl, alkylheteroaryl, alkenylheteroaryl, alkynylheteroaryl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, polycycloalkyl, polycycloalkenyl, and ketyl;

R 6 is unsubstituted or substituted (C 4 -C 12 ) alkyl, (C 1 -C 12 ) alkenyl, (C 1 -C 12 ) alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl, alkylheteroaryl, alkenylheteroaryl, alkynylheteroaryl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, polycycloalkyl, and polycycloalkenyl, or ketyl;

Z 1 and Z 2 are each independently 0 to 4 halo substituents; and

X − is a counterion.

2. The compound of claim 1 wherein Y 1 —Y 2 is CH 2 —CH 2 , γ-β is C═CH, each R′ is H, and each R″ is H.

3. The compound of claim 1 wherein Y 1 —Y 2 is CH 2 —O, γ-β is C═CH, each R′ is H, and each R″ is H.

4. The compound of any one of claim 1 , wherein the compound has a tertiary amino group.

5. The compound of any one of claim 1 , wherein the compound has a quaternary ammonium group.

6. The compound of claim 1 wherein γ-β is C═CH having an (E) conformation.

7. The compound of claim 1 wherein γ-β is C═CH having a (Z) conformation.

8. The compound of claim 1 wherein m is 2.

9. The compound of claim 1 wherein each R′ and each R″ are H.

10. The compound of claim 1 wherein at least one R′ is CH 3 .

11. The compound of claim 1 wherein R 4 and R 5 are each CH 3 .

12. The compound of claim 1 wherein at least one of Z 1 and Z 2 is a halo substituent.

13. The compound of claim 12 wherein at least one of Z 1 and Z 2 is a chloro substituent.

14. The compound of claim 1 wherein X − is a halogen ion.

15. The compound of claim 14 wherein X − is a bromine ion.

16. A pharmaceutical preparation comprising a compound of the formula:

and a pharmaceutically acceptable carrier wherein Y 1 —Y 2 is CH 2 —CH 2 , CH═CH and CH 2 —O;

γ-β is selected from C═CH, CH—CH 2 , and N—CH 2 ;

each R′ and each R″ are independently selected from H and (C 1 -C 8 ) alkyl;

m is an integer ranging from 0 to 7;

each n is an integer ranging from 0 to m;

R 4 is selected from unsubstituted or substituted (C 1 -C 12 ) alkyl, (C 1 -C 12 ) alkenyl, (C 1 -C 12 ) alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl, heteroaryl, alkylheteroaryl, alkenylheteroaryl, alkynylheteroaryl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, polycycloalkyl, polycycloalkenyl, ketyl, and nothing;

R 5 is selected from unsubstituted or substituted (C 1 -C 12 ) alkyl, (C 1 -C 12 ) alkenyl, (C 1 -C 12 ) alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl, heteroaryl, alkylheteroaryl, alkenylheteroaryl, alkynylheteroaryl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, polycycloalkyl, polycycloalkenyl, and ketyl;

R 6 is unsubstituted or substituted (C 4 -C 12 ) alkyl, (C 1 -C 12 ) alkenyl, (C 1 -C 12 ) alkynyl, aryl, alkylaryl, alkenylaryl, alkynylaryl, alkylheteroaryl, alkenylheteroaryl, alkynylheteroaryl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, polycycloalkyl, polycycloalkenyl, or ketyl;

Z 1 and Z 2 are each independently 0 to 4 halo substituents; and

X − is a counterion.

17. The compound according to claim 1 wherein the structure is not of the formula:

wherein R 1 is selected from CH 2 —CH 2 , CH 2 —O, and CH═CH;

γ-β is selected from C═CH, N—CH 2 , and CH—CH 2 ;

m is an integer from 0 to 7;

R 4 is H or R 6 ;

R 5 is H or R 6 ;

R 6 is selected from (C 1 -C 8 ) alkyl, (C 1 -C 8 ) substituted alkyl, (C 1-C 8 ) alkenyl, (C 1 -C 8 ) substituted alkenyl, (C 1 -C 8 ) alkynyl, (C 1 -C 8 ) substituted alkynyl, alkylaryl (wherein the substituents can be (C 1 -C 4 ) alkyl, (C 1 -C 4 ) substituted alkyl, (C 1 -C 4 ) alkenyl, (C 1 -C 4 ) substituted alkenyl, (C 1 -C 4 ) alkynyl, and (C 1 -C 4 ) substituted alkynyl) or R 6 is nothing;

R 7 is H or Cl;

R 8 is H or Cl; and

R 9 is H or Cl.

18. The compound of claim 17 , wherein Y 1 —Y 2 or R 1 is CH 2 —CH 2 , γ-β is C═CH, each R′ is H, and each R″ is H.

19. The compound of claim 17 , wherein Y 1 —Y 2 or R 1 is CH 2 —O, γ-β is C═CH, each R′ is H, and each R″ is H.

20. The compound of claim 17 , wherein the compound has a tertiary amino group.

21. The compound of claim 17 , wherein the compound has a quaternary ammonium group.

22. The compound of claim 17 , wherein γ-β is C═CH having an (E) conformation.

23. The compound of claim 17 , wherein γ-β is C═CH having a (Z) conformation.

24. The compound of claim 17 , wherein m is 2.

25. The compound of claim 17 , wherein R 4 and R 5 are each CH 3 .

26. The compound of claim 17 , wherein X − is a halogen ion.

27. The compound of any one of claims 2 , 3 , or 17 , wherein the compound has a tertiary amino group.

28. The compound of any one of claims 2 , 3 , or 17 , wherein the compound has a quaternary ammonium group.

29. The compound of any one of claim 17 , wherein the compound has a tertiary amino group.

30. The compound of claim 2 , wherein the compound has a quaternary ammonium group.

31. The compound of claim 3 , wherein the compound has a quaternary ammonium group.

32. The compound of claim 17 , wherein the compound has a quaternary ammonium group.