Schizophrenic disorder treatment using combination therapy
Inventors
Granger, Kiri • Barnett, Jennifer
Assignees
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Publication Number
US-12594270-B2
Publication Date
2026-04-07
Expiration Date
Abstract
The present specification disclose a combined therapy comprising one or more activators of an alpha-7 nicotinic acetylcholine receptor activity having 5-HT3 receptor inhibitory activity and one or more activators of 5-HT3 receptor activity for use in treating a schizophrenic disorder as well as methods of treating a schizophrenic disorder by administering a combined therapy comprising one or more activators of an alpha-7 nicotinic acetylcholine receptor activity having 5-HT3 receptor inhibitory activity and one or more activators of 5-HT3 receptor activity.
Core Innovation
The disclosed invention provides a combination therapy for treating a schizophrenic disorder by administering Tropisetron together with Varenicline. The combination pairs an alpha-7 nicotinic acetylcholine receptor (α7 nAChR) activator that has 5-HT3 receptor inhibitory activity with a 5-HT3 receptor activator (agonist). Tropisetron is described as having α7 nAChR/5-HT3 inhibitory activity and Varenicline is described as having 5-HT3 agonist activity with α7 activity.
The background rationale states that α7 agonists fail clinically at least in part due to gastrointestinal side effects mediated by 5-HT3 antagonism. The disclosed combination aims to stimulate gastrointestinal 5-HT3 to improve tolerability while maintaining α7-related therapeutic intent. The document additionally provides definitions of receptor agonist, antagonist, inverse agonist, and combination composition formats including single versus separate compositions, and sequential or simultaneous dosing.
The disclosure further describes therapeutically effective amounts and relative concepts of suboptimal therapeutic amount and non-therapeutic amount compared with an optimal therapeutic effective amount. In vivo latent inhibition studies using rodents are described to evaluate procognitive efficacy and reversal of amphetamine/MK801-induced effects, including safety monitoring via gut motility. The disclosure also references gastrointestinal issues such as constipation in the context of tolerability concerns.
Claims Coverage
The partial content identifies one independent claim (clm-00001) and multiple dependent refinements that add population selection, dosing ranges, composition format, and relative dosing constraints. Across the dependent claims, the key inventive features focus on the specific drug pairing and dosing/composition relationships expressed as therapeutically effective amounts and suboptimal-to-optimal amount relationships.
Treating a schizophrenic disorder using a Tropisetron and Varenicline combination therapy
A method of treating a schizophrenic disorder by administering a combination therapy comprising Tropisetron and Varenicline.
Selecting a schizophrenic disorder subtype for treatment
The method is directed to a schizophrenic disorder selected from schizophrenia, schizophreniform disorder, schizoaffective disorder, or schizotypal personality disorder.
Administering therapeutically effective dose ranges for Tropisetron and Varenicline
Therapeutically effective amounts are administered comprising Tropisetron at about 2 mg to about 75 mg and Varenicline at about 0.25 mg to about 4 mg.
Providing Tropisetron and Varenicline as separate compositions
A first composition contains Tropisetron and a second composition contains Varenicline.
Using suboptimal therapeutic amounts when each drug is administered alone
A therapeutically effective combined dose consists of Tropisetron at a suboptimal therapeutic amount when given alone and Varenicline at a suboptimal therapeutic amount when given alone.
Defining suboptimal amounts relative to an optimal therapeutic effective amount
A suboptimal therapeutic amount is less than 80%, 75%, 70%, 60%, 55%, or 50% of an optimal therapeutic effective amount.
Claim coverage in the partial content centers on administering Tropisetron and Varenicline together to treat a schizophrenic disorder, with dependent features specifying which schizophrenic diagnoses are treated, providing explicit Tropisetron and Varenicline therapeutically effective dose ranges, defining the combination as separate compositions, and constraining the dosing relationship using suboptimal therapeutic amounts relative to an optimal therapeutic effective amount.
Stated Advantages
Improves tolerability by stimulating gastrointestinal 5-HT3 to address gastrointestinal side effects associated with α7 agonists mediated by 5-HT3 antagonism.
Documented Applications
Treatment of a schizophrenic disorder, including schizophrenia subtypes selected from schizophrenia, schizophreniform disorder, schizoaffective disorder, or schizotypal personality disorder.
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