P&U Files In USA For Parkinson's Drug

Pharmacia & Upjohn has filed a New Drug Application in the USA for pramipexole, a drug for treating Parkinson's disease. The compound is one of a new generation of selective dopamine agonists and has extremely specific and potent activity at the D3 receptor. Loss of dopaminergic function in the substantia nigra of the brain is the primary cause of Parkinson's disease.

Currently, the mainstay of therapy for PD is levodopa combined with carbidopa; levodopa is converted into dopamine within the brain, while carbidopa prevents the peripheral breakdown of levodopa, thus effectively extending the duration of drug action. Unfortunately, levodopa almost always loses its efficacy over time and long-term administration is associated with side effects, including involuntary movements, psychosis and hallucinations.

Dopamine receptor agonists such as bromocriptine (Sandoz' Parlodel) and pergolide (Eli Lilly's Permax), tend to be used as second-line therapy in PD. These agents reduce the fluctuations (on-off effects) which are seen with levodopa therapy, but their therapeutic efficacy tends to decline after about six months, particularly in patients with more advanced disease. They also function only as partial agonists at dopamine receptors, and are agonists at the D1A receptor - activity at this receptor has been linked with a tendency to stimulate dyskinesias.