Treatment and management of augmentation in restless legs syndrome
Inventors
Clemens, Stefan • Lallemand, Perrine
Assignees
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Publication Number
US-12220404-B2
Publication Date
2025-02-11
Expiration Date
Abstract
The present invention provides methods of treating Restless Legs Syndrome (RLS) including administering to a subject an effective amount of a dopamine D1 receptor antagonist. Compositions and kits useful for treating RLS are also provided.
Core Innovation
The invention uses the D1 receptor antagonist ecopipam (SCH 39166), alone or with D3 receptor agonists, to treat augmentation associated with restless legs syndrome (RLS) treatment and to restore responsiveness to D3 receptor agonists after reduced responsiveness or increased tolerance. It addresses augmentation and reduced responsiveness associated with prolonged D3 receptor agonism, and identifies treatment of augmentation and restoration or decrease of tolerance as intended outcomes.
The proposed mechanism is that prolonged D3 receptor agonism increases D1 receptor expression and excitability. The document reports that chronic pramipexole exposure is associated with a change in thermal withdrawal latency, that D1 receptor antagonism increases latency and reverses this effect, and that D1 receptor protein expression increases after prolonged D3 receptor agonist exposure.
Claims Coverage
The claim coverage includes two inventive features covering treatment of augmentation associated with restless legs syndrome treatment and restoration of responsiveness or reduction of tolerance to a D3 receptor agonist.
Treating augmentation associated with RLS treatment
The first independent claim covers treating augmentation associated with restless legs syndrome treatment by administering an effective amount of ecopipam. Dependent claims add use with a D3 receptor agonist and describe increased latency to symptom onset at rest, reduced symptom intensity, and reduced expansion of symptoms to the upper limbs and trunk compared with a D3 receptor agonist alone. Named D3 receptor agonists include nafadotride, PD 128907, pramipexole, pergolide, and rotigotine.
Restoring responsiveness to a D3 receptor agonist
The second independent claim covers administering ecopipam after a D3 receptor-mediated reduction in responsiveness or increase in tolerance, while activating a D3 receptor pathway and inhibiting D1 receptor activity, thereby restoring responsiveness or decreasing tolerance to the D3 receptor agonist. Dependent claims specify subjects at risk for or suffering from augmentation and identify named D3 receptor agonists, including nafadotride, PD 128907, pramipexole, pergolide, and rotigotine.
Together, the independent claims cover ecopipam-based treatment of RLS augmentation and ecopipam-based restoration or preservation of responsiveness to D3 receptor agonists after reduced responsiveness or increased tolerance.
Stated Advantages
Treats augmentation associated with restless legs syndrome treatment.
Increases latency to onset of RLS symptoms at rest, reduces symptom intensity, and reduces expansion of symptoms to the upper limbs and trunk compared with a D3 receptor agonist alone.
Restores responsiveness or decreases tolerance to a D3 receptor agonist.
Documented Applications
Treatment of augmentation associated with restless legs syndrome treatment.
Restoration of responsiveness or reduction of tolerance to a D3 receptor agonist after reduced responsiveness or increased tolerance.
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