Use of (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane in the treatment of conditions affected by monoamine neurotransmitters
Inventors
McKINNEY, Anthony Alexander • Bymaster, Frank
Assignees
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Publication Number
US-12042481-B2
Publication Date
2024-07-23
Expiration Date
Abstract
The present invention relates to (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane and pharmaceutical compositions thereof, and methods employing their use in the treatment of conditions affected by monoamine neurotransmitters, including ADHD and substance abuse.
Core Innovation
The invention provides a method and pharmaceutical composition for treating ADHD or a related behavioral disorder in a subject. The composition includes an effective amount of (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, or a pharmaceutically acceptable salt thereof, formulated for sustained delivery in a bi-layer tablet dosage form.
A central aspect is the selection and use of (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane that is substantially free of the corresponding (−) enantiomer, described as an unbalanced triple monoamine reuptake inhibitor targeting NE/DA/5-HT. The document states an inhibition ratio of approximately 1:6:14 and IC50 values reported as approximately 6/38/83 nM for NE/DA/5-HT inhibition, respectively.
The document further connects the compound and formulation to treatment outcomes in ADHD- or behavioral-disorder relevant settings, including rationale based on increased extracellular NE/DA/5-HT in rat brain microdialysis and dose-dependent behavioral effects in animal models. It also characterizes formulation concepts for sustained delivery, including immediate release and slow-release layers.
Claims Coverage
The partial content includes one independent claim covering treating ADHD or a related behavioral disorder using a sustained-delivery bi-layer tablet formulation. The inventive features are centered on the specific (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane (or pharmaceutically acceptable salt) and the bi-layer tablet with immediate and slow-release layers for sustained delivery.
Treating ADHD with a sustained-delivery bi-layer tablet formulation
Administering to a subject in need of treatment for ADHD or a related behavioral disorder a pharmaceutical composition comprising an effective amount of (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt thereof in a bi-layer tablet dosage form for sustained delivery, wherein the bi-layer tablet comprises an immediate release and a slow-release layer.
Overall, the independent claim defines a treatment method for ADHD or related behavioral disorder that uses a bi-layer tablet dosage form for sustained delivery, combining an immediate release layer with a slow-release layer, with the active compound being (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane or a pharmaceutically acceptable salt.
Stated Advantages
Provides sustained delivery for treatment of ADHD or a related behavioral disorder using a bi-layer tablet with an immediate release and a slow-release layer.
Uses an (1R,5S)-(+)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane substantially free of the (−) enantiomer that is described as an unbalanced triple monoamine reuptake inhibitor targeting NE/DA/5-HT.
Documented Applications
Treating ADHD in a subject, including pediatric and adult ADHD, using the sustained-delivery bi-layer tablet dosage form.
Treating a related behavioral disorder, including Oppositional Defiant Disorder and Conduct Disorder, using the same sustained-delivery bi-layer tablet dosage form.
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