Pharmaceutical combination

Abstract

The present invention relates to a pharmaceutical combination for the treatment of schizophrenia and acute manic episodes associated with bipolar disorders, which comprises a compound which is active on a trace amine-associated receptor 1 (TAAR1 agonist) and an antipsychotic drug. This combination can reduce metabolic side effects which appear if using an antipsychotic drug alone.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)[0001]This application is a divisional of U.S. application Ser. No. 13 / 189,600, Filed Jul. 25, 2011, which claims the benefit of European Patent Application No. 10171560.5, filed Aug. 2, 2010, which is hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Schizophrenia is a severe and chronic mental illness, with prevalence estimates ranging from 1.4 to 4.6 per 1000 population.[0003]Schizophrenic disorders and depression are caused by a combination of genetic and environmental factors, which include, for schizophrenia, probable neurodevelopmental abnormalities in gray and white matter structures. Underlying the symptomatic phenomena in both diseases, disturbances in monoaminergic neurotransmission (e.g. serotonin, adrenaline, and noradrenaline) have been proposed.[0004]These pathways are widely present in the CNS and, thus, are potentially capable of influencing many areas involved in emotional processing, cognitio...

AI Technical Summary

Benefits of technology

[0039]The present invention provides a pharmaceutical combination for the treatment of schizophrenia and acute manic episodes associated with bipolar disorders, which comprises a compound that is active on a trace amine-associated receptor 1 (TAAR1 agonist) and an antipsychotic drug. Such a combination can reduce metabolic side effects which appear when using an antipsychotic drug alone.

[0040]A combination of an antipsychotic drug with a trace amine-associated receptor 1 agonist has the potential to reduce the incidence of metabolic syndrome and positive symptoms in schizophrenia as well as acute manic episodes associated with bipolar disorders.

[0041]Based on the above, TAAR1 agonists should be effective agents in the treatment of psychiatric disorders, both directly as well as indirectly by influencing monoaminergic pathways. TAAR1 agonists that have been extensively profiled in non-clinical experiments indicative of antipsychotic, procognitive, antidepressant, and anti-addictive activity, leading to the thought that it may constitute a completely new class of drugs for the treatment of schizophrenia and mood disorders. Based on this profile, TAAR1 agonists may have the potential to treat schizophrenic patients with better efficacy, including ameliorating negative and cognitive symptoms which are not currently treatable with existing therapies, and possibly reducing substance abuse in these patients. Finally, given its beneficial metabolic, anti-diabetic effects, these drugs could provide significant benefits for schizophrenic patients, allowing the control of positive symptoms without increasing metabolic syndrome.

Problems solved by technology

The treatment with antipsychotic drugs, such as olanzapine, may lead to serious side effects.

Cardiometabolic adverse effects, such as weight gain, obesity, hypertension and lipid and glucose abnormalities, are particularly problematic during development because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity and malignancy, especially if used in children and adolescents.

There may be an increased risk of increased blood sugar levels and diabetes with olanzapine as well as the other antipsychotic medications in its class.

Cardiometabolic adverse effects, such as age-inappropriate weight gain, obesity, hypertension, and lipid and glucose abnormalities, are particularly problematic during development because they predict adult obesity, the metabolic syndrome, cardiovascular morbidity, and malignancy,” the authors wrote.

“Moreover, abnormal childhood weight and metabolic status adversely affect adult cardiovascular outcomes via continuation of these risk factors or independent or accelerated mechanisms.”

However, given the risk for weight gain and long-term risk for cardiovascular and metabolic problems, the widespread and increasing use of atypical antipsychotic medications in children and adolescents should be reconsidered.”

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