Bifeprunox
Encyclopedia
Bifeprunox is a novel atypical antipsychotic
agent which, along with SLV313, aripiprazole
, and SSR-181507 combines minimal D2 receptor agonism with 5-HT receptor agonism.
Bifeprunox has a novel mechanism of action. Conventional antipsychotics are classed into typical and atypical. The typical antipsychotics, such as chlorpromazine
and haloperidol
are potent D2 receptor antagonist
s. The atypical antipsychotic
s started with clozapine
, these are classified as multireceptor interacting compounds, acting as an agonist towards 5-HT1A and an antagonist towards D2 receptors among other 5-HT and DA receptors. Bifeprunox and other novel atypical antipsychotics will instead of antagonizing D2 receptors, will act as partial agonists, as well as antagonists towards 5-HT1A receptors.
In a multi-center, placebo-controlled study, 20 mg of bifeprunox was found to be significantly more effective than placebo at reducing symptoms of schizophrenia, with a low incidence of side effects.
An NDA for Bifeprunox was filed with the U.S. Food and Drug Administration in January 2007. The FDA rejected the application in August 2007. In June 2009, Solvay and Lundbeck decided to cease development because "efficacy data did not support pursuing the existing development strategy of stabilisation of non-acute patients with schizophrenia."
Tulp, M. T. M.; van der Heyden, J. A. M.; Kruse, C. G.; Bioorg. Med. Chem. Lett.
2001, 11, 2345.
http://dx.doi.org/10.1016/S0960-894X(01)00425-5
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
agent which, along with SLV313, aripiprazole
Aripiprazole
Aripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
, and SSR-181507 combines minimal D2 receptor agonism with 5-HT receptor agonism.
Bifeprunox has a novel mechanism of action. Conventional antipsychotics are classed into typical and atypical. The typical antipsychotics, such as chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
and haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
are potent D2 receptor antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
s. The atypical antipsychotic
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
s started with clozapine
Clozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
, these are classified as multireceptor interacting compounds, acting as an agonist towards 5-HT1A and an antagonist towards D2 receptors among other 5-HT and DA receptors. Bifeprunox and other novel atypical antipsychotics will instead of antagonizing D2 receptors, will act as partial agonists, as well as antagonists towards 5-HT1A receptors.
In a multi-center, placebo-controlled study, 20 mg of bifeprunox was found to be significantly more effective than placebo at reducing symptoms of schizophrenia, with a low incidence of side effects.
An NDA for Bifeprunox was filed with the U.S. Food and Drug Administration in January 2007. The FDA rejected the application in August 2007. In June 2009, Solvay and Lundbeck decided to cease development because "efficacy data did not support pursuing the existing development strategy of stabilisation of non-acute patients with schizophrenia."
Chemistry
Feenstra, R. W.; de Moes, J.; Hofma, J. J.; Kling, H.; Kuipers, W.; Long, S. K.;Tulp, M. T. M.; van der Heyden, J. A. M.; Kruse, C. G.; Bioorg. Med. Chem. Lett.
2001, 11, 2345.
http://dx.doi.org/10.1016/S0960-894X(01)00425-5