An h3 receptor antagonist for use in the treatment of alzheimer's disease

Abstract

This disclosure relates to methods of using 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide in a disease modifying therapy of Alzheimer's disease, other tauopathies and related neurodegenerative diseases.

What is claimed is: 
     
         1 . Compound 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or a pharmaceutically acceptable salt thereof for use in the prevention or the delay of the disease progression of a tauopathy or related neurodegenerative disease in a patient. 
     
     
         2 . Compound for use according to  claim 1 , in which abnormal tau hyperphosphorylation or abnormal tau aggregation in a patient is inhibited. 
     
     
         3 . Compound for use according to  claim 1 , in which the level of phosphorylated tau protein in said patient having a tauopathy or related neurodegenerative disease is reduced. 
     
     
         4 . Compound for use according to  claim 1 , in which formation of neurofibrillary tangles in said patient is inhibited. 
     
     
         5 . Compound for use according to  claim 1 , in which the level of neurofibrillary tangles in a neuronal cell in said patient is inhibited. 
     
     
         6 . Compound for use according to  claim 1 , in which cytoskeleton dysfunction or perturbation of other tau-dependent functions are slowed or stopped. 
     
     
         7 . Compound for use according to  claim 1 , in which the level of phosphorylated tau and tau in the patient's cerebrospinal fluid is reduced. 
     
     
         8 . Compound for use according to  claim 1 , in which tau aggregates in said patient are disrupted or dissolved. 
     
     
         9 . Compound for use according to  claim 1 , in which phosphorylation of tau protein in a neuron, glial cell or Lewy body in said patient is inhibited or reduced. 
     
     
         10 . Compound for use according to  claim 9 , in which the tau protein is microtubule-associated tau protein. 
     
     
         11 . Compound for use according to  claim 10 , in which the tau protein is in a neurofibrillary tangle. 
     
     
         12 . Compound for use according to  claim 1 , in which hyperphosphorylation of tau protein is inhibited or prevented. 
     
     
         13 . Compound for use according to  claim 1  in which the tauopathy or related neurodegenerative disease is Alzheimer's disease. 
     
     
         14 . Compound for use according to  claim 1  in which the tauopathy or related neurodegenerative disease is mild-to-moderate Alzheimer's disease. 
     
     
         15 . Compound for use according to  claim 1  in which the tauopathy or related neurodegenerative disease is moderate-to-severe Alzheimer's disease. 
     
     
         16 . Compound for use according to  claim 1  in which the tauopathy or related neurodegenerative disease is preclinical Alzheimer's disease. 
     
     
         17 . Compound for use according to  claim 1  in which the tauopathy or related neurodegenerative disease is mild cognitive impairment. 
     
     
         18 . Compound for use according to  claim 1  in which 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or pharmaceutically acceptable salt thereof is administered at least one time a day for a prolonged duration. 
     
     
         19 . Compound for use according to  claim 1  in which 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or pharmaceutically acceptable salt thereof is 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide difumarate monohydrate. 
     
     
         20 . Compound for use according to  claim 1  in which 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide or pharmaceutically acceptable salt thereof is to be administered at least one time per day over a prolonged period.