Antipsychotic - bifeprunox mesilate
The World Health Organization (WHO) estimates that 24 million people around the world suffer from schizophrenia. It is a severe condition that often results in a breakdown in mental processes, along with a loss of contact with reality.
The World Health Organization (WHO) estimates that 24 million people around the world suffer from schizophrenia. It is a severe condition that often results in a breakdown in mental processes, along with a loss of contact with reality.
All patients experience positive symptoms some of the time, such as bizarre thoughts, auditory hallucinations, delusions and irrational fears, and most also have negative symptoms, including lack of motivation, social withdrawal, lack of energy and apathy.
Historically, antipsychotic drugs such as chlorpromazine or haloperidol have been used for treatment, but serious side-effects are common, such as cognitive disorders, weight gain and impaired motor function. Atypical antipsychotic drugs have been introduced more recently, which, although more expensive, show reduced side-effect profiles and could therefore improve dosing compliance.
A new antipsychotic discovered by Solvay is being developed by Lundbeck and has been licensed to Wyeth. Bifeprunox is a full spectrum D2 partial agonist and 5-HT1A agonist.1 It antagonised dopamine agonist-induced behaviours but also stimulated dopamine receptors, even when dopaminergic tone was low or dopamine receptors were upregulated, and showed a low propensity to induce motor and metabolic side-effects.
An initial open-label dose-escalating study was carried out in six healthy male volunteers.2 Positron emission tomography with 11-C reaclopride was used to determine the D2 receptor occupancy and changes in plasma prolactin at two and 24 hours after oral dosing with 0.25, 2, 10 or 25mg bifeprunox. D2 receptor occupancy plateaued at a dose of 10mg, and remained at about 79% 24 hours after dosing. Once-a-day dosing was therefore used in ensuing studies.
In a placebo-controlled dose-finding Phase II study in patients with schizophrenia, it was shown to be well tolerated with no incidences of weight gain or cardiovascular side-effects. Various further Phase II and III studies are under way in patients with schizophrenia, along with investigations for use as a treatment for schizoaffective and bipolar disorder.