Duke University

Tatyana D Sotnikova

Marc G Caron

Raul R Gainetdinov

David M Gooden

Martin Beaulieu

Julie A Pollock

Dewey G McCafferty

Xiaodong Zhang

The present invention is directed to a method of treating Parkinson's disease using arylcyclopropylamine compounds. The arylcyclopropylamine compounds have the following formula wherein R, R, R, R, Rand Rare described herein.

Methods of treatment using arylcyclopropylamine compounds

A method of treating a subject for Parkinson's disease comprises administering said subject a phenylisopropylamine in an amount effective to treat said Parkinson's disease. In some embodiments the method is used to treat at least a motor symptom of Parkinson's disease; in some embodiments the method is used to treat at least a non-motor symptom of Parkinson's disease.

Antiparkinsonian action of phenylisopropylamines

Recombinant or transgenic non-human mammals are described having a mutant tryptophan hydroxylase 2 (Tph2) gene resulting in altered synthesis of 5-hydroxytryptophan and serotonin in the brain. In some embodiments the mutant tryptophan hydroxylase 2 gene contains mouse R439H and/or P447R functional mutations, or their corresponding mutations in other species. Congenic non-human mammals having mutant tryptophan hydroxylase 2 genes are also provided. Methods of screening a compound for serotonergic activity or activity in treating a serotonergic neurotransmission dysregulation disorder are provided, which include administering a test compound to a recombinant non-human mammal and then detecting the presence or absence of serotonergic activity, or activity in treating a serotonergic neurotransmission dysregulation disorder, in the mammal. A cell such as a nerve cell (e.g., a central nervous system neuron) isolated from a transgenic or congenic mammal is also disclosed, along with cell cultures containing these cells.

Transgenic mice carrying functional single nucleotide polymorphisms in brain-specific tryptophan hydroxylase

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Chapel Hill, NC, United States of America

Tatyana D Sotnikova