Pharmaceutical Compositions and Methods for Effecting Dopamine Release

Abstract

Patients susceptible to or suffering from disorders, such as central nervous system disorders, which are characterized by an alteration in normal neurotransmitter release, such as dopamine release (e.g., Parkinsonism, Parkinson's Disease, Tourette's Syndrome, attention deficient disorder, or schizophrenia), are treated by administering a 1-aza-2-(3-pyridyl)bicyclo[2.2.1]heptane, a 1-aza-2-(3-pyridyl)bicyclo[2.2.2]octane, a 1-aza-2-(3-pyridyl)bicyclo[3.2.1]octane, a 1-aza-2-(3-pyridyl)bicyclo[3.2.2]nonane, a 1-aza-7-(3-pyridyl)bicyclo[2.2.1]heptane, a 1-aza-3-(3-pyridyl)bicyclo[3.2.2]nonane, or a 1-aza-7-(3-pyridyl)bicyclo[3.2.2]nonane. The compounds can exist as individual stereoisomers, racemic mixtures, diastereomers and the like.

1 . A compound of the general formula:  
     
       
         
         
             
             
         
       
       wherein A, A′, A″ and A″′ individually are substituent species selected from the group consisting of —H, —F, —Cl, —Br, —I, —R′, —NR′R″, —CF 3 , —OH, —CN, —NO 2 , —C 2 R′, —SH, —SCH 3 , —N 3 , —SO 2 CH 3 , —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH 2 ) q OR′, —OC(═O)R′, —OC(═O)NR′R″, and —NR′C(═O)OR′,  
       R is a substituent species selected from the group consisting of —F, —Cl, —Br, —I, —R′, —NR′R″, —CF 3 , —OH, —CN, —NO 2 , —C 2 R′, —SH, —SCH 3 , —N 3 , —SO 2 CH 3 , —OR′, —SR′, —C(═O)NR′R″, —NR′C(═O)R′, —C(═O)R′, —C(═O)OR′, —(CH 2 ) q OR′, —OC(═O)R′, —OC(═O)NR′R″, and —NR′C(═O)OR′,  
       where R′ and R″ are individually hydrogen C 1 -C 10  alkyl, or an aromatic group-containing species;  
       q is an integer from 1 to 6.  
       m, n and p are individually 0, 1 or 2, and the sum of p plus m is 1 or 2 when n is 0; j is an integer from 0 to 5;  
       and the wavy line in the structure represents that, depending upon the value of each of m, n, and p, the stereochemistry of the carbon at which the azabicyclic ring is attached to the pyridine ring can be either R or S, and the compound can be either the exo or endo diastereomer.