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 method for reducing dopaminergic agent-induced dyskinesia comprising administering to a human being treated with said dopaminergic agent an amount of nicotine sufficient to reduce dyskinesia induced by said dopaminergic agent, wherein said amount of nicotine is administered such that nicotine or a nicotine metabolite reaches a critical concentration of about 1 ng/ml to about 20 ng/ml. 
     
     
         154 . The method of  claim 153  wherein said critical concentration is reached about one hour to about three hours after the dopaminergic agent reaches the bloodstream or brain. 
     
     
         155 . The method of  claim 153  wherein said critical concentration is reached about one hour to about three hours before the dopaminergic agent reaches the bloodstream or brain. 
     
     
         156 . The method of  claim 153  wherein said critical concentration is reached at from about one hour to about a minute before the dopaminergic agent-induced dyskinesia reaches a peak. 
     
     
         157 . The method of  claim 153  wherein the amount of nicotine is sufficient to reduce said dyskinesia at least about 30%. 
     
     
         158 . The method of  claim 153  wherein said dyskinesia is induced by a Parkinson's disease treatment. 
     
     
         159 . The method of  claim 153  wherein said dopaminergic agent comprises a dopamine precursor or a dopamine receptor agonist. 
     
     
         160 . The method of  claim 153  wherein said dopaminergic agent comprises levodopa, bromocriptine, pergolide, pramipexole, cabergoline, ropinirole, apomorphine or a combination thereof. 
     
     
         161 . The method of  claim 160  wherein said dopaminergic agent is levodopa. 
     
     
         162 . The method of  claim 153  wherein said subject suffers from Parkinson's disease. 
     
     
         163 . The method of  claim 153  wherein said administration comprises a single daily dose of nicotine. 
     
     
         164 . The method of  claim 153  wherein said administration comprises multiple daily doses of nicotine. 
     
     
         165 . The method of  claim 153  comprising administering at least one dose of nicotine in a 24-hour period, wherein said nicotine is present at about 6 milligrams or less per dose. 
     
     
         166 . The method of  claim 165  wherein said nicotine is present at about 4 milligrams or less per dose. 
     
     
         167 . The method of  claim 165  wherein said nicotine is present at about 2 milligrams or less per dose. 
     
     
         168 . The method of  claim 165  wherein said nicotine is present at about 1 milligrams or less per dose. 
     
     
         169 . The method of  claim 153  wherein said amount of nicotine administered in a 24-hour period is about 15 milligrams. 
     
     
         170 . The method of  claim 153  wherein said amount of nicotine administered in a 24-hour period is about 8 milligrams. 
     
     
         171 . The method of  claim 153  wherein said amount of nicotine administered in a 24-hour period is about 3 milligrams. 
     
     
         172 . The method of  claim 153  wherein said nicotine is administered orally. 
     
     
         173 . The method of  claim 172  wherein said nicotine is administered in a solid form. 
     
     
         174 . The method of  claim 153  wherein the dopaminergic agent is being administered for the treatment of Parkinson's disease or Parkinsonism in the human and the effective amount of the dopaminergic agent is 100% to 75% of the effective amount when the dopaminergic agent is administered without the nicotine. 
     
     
         175 . The method of  claim 153  wherein said dopaminergic agent is being administered for the treatment of Parkinson's disease or Parkinsonism in the human and the amount of the dopaminergic agent administered is not reduced after nicotine administration. 
     
     
         176 . The method of  claim 153  wherein the human is suffering from said dopaminergic agent-induced dyskinesia. 
     
     
         177 . The method of  claim 153  wherein said amount of nicotine is maintained for a period of more than six months. 
     
     
         178 . The method of  claim 153  wherein said amount of nicotine is maintained for a period of more than one year.