Methods and compositions for reduction of side effects of therapeutic treatments

Abstract

The invention provides compositions and methods utilizing a nicotinic receptor modulator, e.g., to reduce or eliminate a side effect associated with dopaminergic agent treatment. In some embodiments, the invention provides compositions and methods utilizing a combination of a dopaminergic agent and a nicotinic receptor modulator that reduces or eliminates a side effect associated with dopaminergic agent treatment.

1 - 152 . (canceled) 
   
   
       153 . A pharmaceutical composition for transdermal administration comprising nicotine or other nicotinic receptor agonist and a pharmaceutically acceptable carrier, wherein nicotine or other nicotinic receptor agonist is present at about 12 mg or less and wherein the composition is formulated for a single dose. 
   
   
       154 . The composition of  claim 153  wherein the single dose is a daily dose. 
   
   
       155 . The composition of  claim 153  wherein the nicotine is present at about 10 mg, at about 8 mg, at about 6 mg, at about 4 mg, at about 2 mg, at about 1 mg, or at about 0.5 mg. 
   
   
       156 . The composition of  claim 153  wherein the nicotinic receptor agonist is selected from the group consisting of nicotine, conotoxinMIl, epibatidine, A-85380, cytisine, lobeline, anabasine, SIB-1508Y, SIB-1553A, ABT-418, ABT-594, ABT-894, TC-2403, TC-2559, RJR-2403, SSR18071 1, GTS-21 and varenicline 
   
   
       157 . The composition of  claim 153  wherein the composition further comprises a second agent. 
   
   
       158 . The composition of  claim 157  wherein the second agent is a dopaminergic agent. 
   
   
       159 . The composition of  claim 158  wherein the dopaminergic agent is levodopa, bromocriptine, pergolide, pramipexole, cabergoline, ropinorole, apomorphine or a combination thereof. 
   
   
       160 . The composition of  claim 158  wherein the dopaminergic agent is levodopa. 
   
   
       161 . The composition of  claim 157  wherein the composition comprises a third agent. 
   
   
       162 . The composition of  claim 161  wherein the third agent is selected from the group consisting of amantadine, carbidopa and entacapone. 
   
   
       163 . A method of treating a motor disorder in a subject comprising transdermally administering to the subject nicotine or other nicotinic receptor agonist, wherein the dose of nicotine or other nicotinic receptor agonist is at least about 5 mg per dose. 
   
   
       164 . The method of  claim 163  wherein the dose is formulated for a single dose administration. 
   
   
       165 . The method of  claim 163  wherein the single dose is a daily dose. 
   
   
       166 . The method of  claim 163  wherein the single dose is administered once, twice, thrice, four, or five times in a 24-hour period. 
   
   
       167 . The method of  claim 166  wherein a maximum of 25 mg of nicotine is administered in the 24-hour period. 
   
   
       168 . The method of  claim 163  wherein the subject is administered the nicotine or other nicotinic receptor agonist for at least 6 months. 
   
   
       169 . The method of  claim 163  wherein the motor disorder is Parkinson's disease. 
   
   
       170 . The method of  claim 163  wherein the motor disorder is dyskinesia, wherein said dyskinesia is dopaminergic-agent induced. 
   
   
       171 . The method of  claim 163  wherein the nicotine is at least about 6 mg, at least about 7 mg, at least about 8 mg, at least about 9 mg, at least about 10 mg, at least about 11 mg, or at least about 12 mg per dose. 
   
   
       172 . The method of  claim 163  wherein the nicotinic receptor agonist is selected from the group consisting of nicotine, conotoxinMIl, epibatidine, A-85380, cytisine, lobeline, anabasine, SIB-1508Y, SIB-1553A, ABT-418, ABT-594, ABT-894, TC-2403, TC-2559, RJR-2403, SSR180711, GTS-21 and varenicline. 
   
   
       173 . The method of  claim 163  wherein the composition further comprises a second agent. 
   
   
       174 . The method of  claim 173  wherein the second agent is a dopaminergic agent. 
   
   
       175 . The method of  claim 174  wherein the dopaminergic agent is levodopa, bromocriptine, pergolide, pramipexole, cabergoline, ropinorole, apomorphine or a combination thereof. 
   
   
       176 . The method of  claim 174  wherein the dopaminergic agent is levodopa. 
   
   
       177 . The method of  claim 173  wherein the composition comprises a third agent. 
   
   
       178 . The method of  claim 177  wherein the third agent is selected from the group consisting of amantadine, carbidopa and entacapone.