Bridged heterocyclic compounds and methods of use

1. A compound of the formula (E):

where:

R 1 is H, hydroxyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8 perhaloalkoxy, alkoxy, aryloxy, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;

R 2 is H, hydroxyl, alkoxy or substituted or unsubstituted C 1 -C 8 alkyl;

each R 3a and R 3b is independently H, substituted or unsubstituted C 1 -C 8 alkyl, halo, cyano, nitro, hydroxyl, alkoxy, substituted or unsubstituted amino, cycloalkyl, aryl, heteroaryl, heterocyclyl, acylamino or acyloxy or R 3a and R 3b are taken together to form a cycloalkyl moiety or a carbonyl moiety;

each X 7 , X 8 , X 9 and X 10 is independently N or CR 4 ;

p is 1 or 2;

each R 4 is independently H, hydroxyl, nitro, cyano, halo, C 1 -C 8 perhaloalkyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8 perhaloalkoxy, C 1 -C 8 alkoxy, aryloxy, carboxyl, thiol, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;

each R 8a , R 8b , R 8c and R 8d is independently H, hydroxyl, alkoxy, halo, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 2 -C 8 alkenyl, C 1 -C 8 perhaloalkyl, carboxyl, carbonylalkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or is taken together with a geminal R 8(a-d) to form a substituted or unsubstituted methylene moiety or a moiety of the formula —OCH 2 CH 2 O—, or is taken together with a geminal R 8(a-d) and the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or is taken together with a vicinal R 8(a-d) and the carbon atoms to which they are attached to form a substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkenyl, or substituted or unsubstituted heterocyclyl moiety, or is taken together with a vicinal R 8(a-d) to form a bond provided when an R 8 taken together with a vicinal R 8(a-d) to form a bond, the geminal R 8(a-d) is other than hydroxyl;

wherein at least one of R 8a , R 8b , R 8c and R 8d is alkoxy, halo, C 1 -C 8 alkyl substituted with an acylamino, carbonylalkoxy or carboxyl moiety, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or is taken together with a geminal R 8(a-d) to form a moiety of the formula —OCH 2 CH 2 O—;

represents a single or double bond, provided that when is a double bond, R 8a and R 8c are absent and R 8b and R 8d are other than OH;

R 10 is H, hydroxyl, alkoxy or a substituted or unsubstituted C 1 -C 8 alkyl;

Q is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted C 3 -C 8 cycloalkyl, substituted or unsubstituted C 3 -C 8 cycloalkenyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted amino, alkoxy, aminoacyl, acyloxy, carboxyl, carbonylalkoxy, cyano, alkynyl, aminocarbonylalkoxy or acylamino;

or a salt or solvate thereof.

2. A compound selected from the group consisting of compounds L-1 to L-61, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 or 2 , wherein the compound modulates at least one of the following receptors: adrenergic receptor, serotonin receptor, dopamine receptor and histamine receptor.

4. A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of claim 1 or 2 .

5. A pharmaceutical composition comprising a compound of claim 1 or 2 and a pharmaceutically acceptable carrier.

6. A kit comprising a compound of claim 1 or 2 and instructions for use in the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder.

7. A compound of the formula (L-1):

wherein:

R 1 is H, hydroxyl, nitro, cyano, halo, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C 1 -C 8 perhaloalkoxy, alkoxy, aryloxy, carboxyl, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy;

R 2 is H, hydroxyl, nitro, cyano, halo, C 1 -C 8 perhaloalkyl, substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 2 -C 8 alkenyl, substituted or unsubstituted C 2 -C 8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C 1 -C 8 perhaloalkoxy, C 1 -C 8 alkoxy, aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl;

X is OH, H, C 1 -C 8 unsubstituted alkyl or is taken together with Y to form a cyclic moiety of the formula —OCH 2 CH 2 O—;

Y is halo; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; C 1 -C 8 alkyl substituted with a carbonylalkoxy, carboxyl or acylamino moiety; or is taken together with X to form a cyclic moiety of the formula —OCH 2 CH 2 O—; and

R 3 is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl;

or a salt or solvate thereof.

8. The compound of claim 7 , wherein the compound is of the formula (L-2):

or a salt or solvate thereof.

9. The compound of claim 7 , wherein the compound is of the formula (L-3):

or a salt or solvate thereof.

10. The compound of claim 7 , wherein the compound is of the formula (L-4):

wherein R 4 is an unsubstituted C 1 -C 8 alkyl; or a salt or solvate thereof.

11. The compound of claim 7 , wherein the compound is of the formula (L-5):

or a salt or solvate thereof.

12. The compound of claim 7 , wherein the compound is of the formula (L-6):

or a salt or solvate thereof.

13. The compound of claim 7 , wherein the compound is of the formula (L-7):

or a salt or solvate thereof.

14. The compound of claim 7 , wherein the compound is of the formula (L-8):

or a salt or solvate thereof.

15. A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier.

16. A kit comprising a compound claim 7 and instructions for use in the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder.