[Pharmacological profiles and clinical effects of antiparkinsonian agent, pramipexole]

Pramipexole hydrochloride (pramipexole) is a nonergot dopamine D(2) agonist, and the S(-)enantiomer is used for the treatment of Parkinson's disease (PD). Pramipexole possessed the highest affinity with the D(3) subtype among the D(2) receptor subfamily members (D(2), D(3), D(4)), lacking affinity with the D(1) and D(5) subtype. Pramipexole ameliorated the motor disturbances in PD animal models, induced contralateral rotational behavior reflecting post-synaptic D(2) receptor stimulation in the striatum, and showed a variety of neuroprotective effects in vitro and in vivo experimental systems. The neuroprotective effects of pramipexole seemed to be derived from several mechanisms: stimulation of D(2) autoreceptor, stimulation of D(3) receptor, inhibition of oxidative reaction and following radical production, increase of Bcl-2 protein and inhibition of apoptotic cell death, and production of neurotrophic factor. Clinical efficacy of pramipexole both in monotherapy and combined use with L-DOPA were confirmed evaluating by UPDRS (Unified Parkinson's Disease Rating Scale) II (Activities of daily living) and III (Motor), in the results of clinical studies mainly performed in USA and European countries and partly in Japan. In addition, patients initially treated with pramipexole demonstrated reduction in problematic symptoms and in loss of striatal [(123)I]2beta-carboxymethoxy-3beta-(4-idodophenyl)tropan uptake, a marker of dopamine neuron degeneration, compared with those initially treated with L-DOPA.