Selective serotonin receptor inverse agonists as therapeutics for disease

Abstract

Disclosed herein are pharmaceutical compositions comprising an inverse serotonin receptor agonist or a serotonin receptor antagonist and an anti-psychotic agent. Disclosed herein are also methods of treating psychotic disorders using the disclosed pharmaceutical compositions.

Description

RELATED APPLICATIONS [0001] This application is a continuation-in-part of the application entitled “Selective Serotonin Receptor Inverse Agonists as Therapeutics for Disease,” filed on May 21, 2004 by David M. Weiner, Robert E. Davis, and Mark R. Brann, attorney docket number ACADIA.051A, which is incorporated herein in its entirety.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The present invention relates to novel combinations of compounds that are effective as therapeutic agents in the treatment of depression, mania, or social phobia, and other psychotic disorders. The combinations include inverse serotonin agonists and another antidepressant, anti-maniac, anti-phobia, or antipsychotic agent. [0004] 2. Description of the Related Art [0005] Serotonin or 5-hydroxytryptamine (5-HT) plays a significant role in the functioning of the mammalian body. In the central nervous system, 5-HT is an important neurotransmitter and neuromodulator that is implicated in such ...

AI Technical Summary

Benefits of technology

[0017] Also disclosed herein is a method of treating a disorder in a patient, the disorder selected from the group consisting of depression, mania, social phobia, psychosis, and a neuropsychiatric disorder, the method comprising: identifying a patient in need of the treatment, and administering to the patient a therapeutically effective amount of a combination of a first compound and a second compound, the first compound selected from the group consisting of an inverse agonist of a serotonin receptor, an antagonist of a serotonin receptor, and pharmaceutically acceptable salts thereof, as described above and the second compound selected from the group consisting of a SSRI, a SNRI, a MAO-I, a TCA, an antipsychotic agent, a norepinephrine reuptake inhibitor, a dopamine agonist, an anti-insomnia drug, an anti-manic drug, an anti-phobia drug, the compound of Formula (II):

Problems solved by technology

It has been estimated that the total financial cost for the diagnosis, treatment, and lost societal productivity of individuals affected by this disease exceeds 2% of the gross national product (GNP) of the United States.

Antipsychotics are effective in ameliorating positive symptoms (e.g., hallucinations and delusions), yet they frequently do not improve negative symptoms (e.g., social and emotional withdrawal, apathy, and poverty of speech).

Use of these compounds is limited, however, by their side effect profiles.

Nearly all of the “typical” or older generation compounds have significant adverse effects on human motor function.

The high degree of genetic and pharmacological homology between these receptor subtypes has hampered the development of subtype-selective compounds, as well as the determination of the normal physiologic or pathophysiologic role of any particular receptor subtype.

Unfortunately, it is likely that antagonism of dopamine D2 receptors also mediates the extrapyramidal side effects.

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