Neuroprotective effects of D3 dopamine receptor agonists

The effects of Dg receptor activation are unresolved at this time, but may have practical implications in the treatment of Parkinson's disease (PD). A s a result of assessing the neuroprotective effects of the direct-acting D- 3 preferring dopamine (DA) agonist pramipexole (PPX), we have observed that drugs which psossess Dg affinity increase the production of a DA neurotrop hic factor in tissue culture. This molecule is increased by treatment with PPX, is constitutively produced by DA neurons in culture, and possesses a m olecular weight of approximately 35 kDa. It is hypothesized that this molec ule may be the so-called DA autotrophic factor referred to by many authors over the past two decades. interestingly, the protein is oxidant-labile and , therefore, D-3 agonists which increase its production and also possess an tioxidant capacity would provide unique neuroprotective benefits to patient s with PD. However, many questions remain. Although the data supporting thi s notion are strong, it is clear that other unknown characteristics of DA a gonists, including increased production of anti-apoptotic proteins, are als o involved. This manuscript will review this concept in the context of tiss ue culture strategies of neuroprotection. Although no conclusion can be mad e at this time, it is clear that direct comparisons of the neuroprotective effects of direct-acting DA agonists in mesencephalic culture can provide c onsiderable insight into the mechanistic actions of anti-dopaminergic drugs . (C) 2001 Elsevier Science Ltd. All rights reserved.