Combinations of serotonin receptor agonists for treatment of movement disorders
Inventors
Hansen, John Bondo • Thomsen, Mikael S.
Assignees
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Publication Number
US-10632116-B2
Publication Date
2020-04-28
Expiration Date
Abstract
The present invention relates to the use of 5-HT1 agonists in pharmaceutical compositions, compounds and methods for treatment of movement disorders related to neurological dysfunctions. The invention is particularly relevant for treatment of patients suffering from tardive dyskinesia, Parkinson's disease and associated disorders thereof. Kits of parts comprising the 5-HT1 agonist compounds or pharmaceutical compositions according to the present invention, as well as methods of preparation are also provided by the present invention.
Core Innovation
The disclosure describes a method for treatment or alleviation of a movement disorder by administration of a synergistically effective amount of zolmitriptan, or a pharmaceutically acceptable salt, together with a synergistically effective amount of buspirone, or a pharmaceutically acceptable salt, to an individual in need thereof. The movement disorders are selected from ataxia, dystonia, Huntington's disease, Rett syndrome, Tourette syndrome, Wilson's disease, Machado-Joseph disease, restless leg syndrome and spasmodic torticollis.
The background problem addressed is that movement disorders are associated with altered neurotransmitter systems, including dopamine-linked changes, and that L-DOPA therapy in Parkinson's disease is associated with abnormal involuntary movements. The disclosure frames the need for treatments that reduce these movement disorder manifestations while maintaining overall motor performance and coordination.
The disclosure further describes combinations in which serotonin 5-HT1A agonists such as buspirone are combined with 5-HT1B/5-HT1D agonists such as triptans, including zolmitriptan and frovatriptan. It also describes optional inclusion of 5-HT1F agonists and additional second active ingredients such as dopamine/L-DOPA and PD adjuncts including carbidopa or benserazide and COMT inhibitors.
Claims Coverage
The independent claim covers a synergistic co-administration regimen combining zolmitriptan and buspirone for treatment or alleviation of specified movement disorders. The inventive focus is the synergistically effective dosing and co-administration of the two agents, with further refinements provided in dependent claims via dose ranges and optional additional active ingredients.
Synergistic co-administration of zolmitriptan and buspirone
A method comprising one or more steps of administration of a synergistically effective amount of a pharmaceutical composition comprising zolmitriptan, or a pharmaceutically acceptable salt thereof, and one or more steps of administration of a synergistically effective amount of buspirone, or a pharmaceutically acceptable salt thereof, to an individual in need thereof, for movement disorders selected from ataxia, dystonia, Huntington's disease, Rett syndrome, Tourette syndrome, Wilson's disease, Machado-Joseph disease, restless leg syndrome and spasmodic torticollis.
Overall, the claims coverage centers on treating or alleviating specified movement disorders by co-administering zolmitriptan and buspirone using synergistically effective amounts, with dependent claims further specifying particular daily dose ranges and, in some variations, optional additional active ingredients.
Stated Advantages
Reduces abnormal involuntary movements/dyskinesia in L-DOPA/6-OHDA rat models.
Shows no significant impairment of motor performance/coordination in the preclinical examples.
Indicates reduced central dopamine levels in the described preclinical and imaging discussions.
Documented Applications
Treatment or alleviation of movement disorders selected from ataxia, dystonia, Huntington's disease, Rett syndrome, Tourette syndrome, Wilson's disease, Machado-Joseph disease, restless leg syndrome and spasmodic torticollis.
Use in Parkinson's disease and L-DOPA-induced dyskinesia, including effects discussed in L-DOPA/6-OHDA rat model and reserpine-induced vacuous chewing movements model.
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