Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist

S32504, a Novel Naphtoxazine Agonist at Dopamine D3/D2 Receptors: II. Actions in Rodent, Primate, and Cellular Models of Antiparkinsonian Activity in Comparison to Ropinirole

“…By analogy to other D 2 /D 3 agonists, such as pramipexole , the neurotoxic effects of MPP ϩ in transformed SH-SY5Y cells were concentration-dependently and stereospecifically abrogated by S32504 compared with S32601. Ropinirole protects dopaminergic neurones from 6-OHDA in mice in vivo (Iida et al, 1999) and delays dopaminergic neuron degeneration in Parkinson patients (Whone et al, 2003). However, in the present model, it was only weakly active, confirming our earlier work (Joyce et al, 2003b) and an independent study of a mesencephalic cell line .…”

Driving GDNF expression: The green and the red traffic lights

“…In this situation, dopamine receptor agonists, mimicking endogenous dopamine, promote neuroprotection through an increase in GDNF expression. Dopamine receptor agonists protect mouse striatal neurons against 6-hydroxydopamine (6-OHDA) toxicity (Iida et al, 1999), and neuroblastoma SH-SY5Y cells and mesencephalic cultures from the toxicity of 1-methyl-4-phenylpyridinium (MPP + ), the active metabolite of MPTP (Presgraves et al, 2004). D2 agonists are also effective against the excitotoxicity evoked by glutamate agonists in mesencephalic neurons (Sawada et al, 1998b).…”

“…D2 agonists are also effective against the excitotoxicity evoked by glutamate agonists in mesencephalic neurons (Sawada et al, 1998b). Although other mechanisms have been proposed, such as the induction of antioxidant defences (Iida et al, 1999), the neuroprotection afforded by dopamine or dopamine receptor agonists has been associated with their ability to promote the expression of several neurotrophic factors. In fact, D3 receptor preferring agonists protect mesencephalic neurons against a MPP + lesion by increasing the secretion of both GDNF and BDNF (Du et al, 2005).…”

Antiparkinsonian Drugs and Their Neuroprotective Effects.

“…75,76) Ropinirole, a non-ergot D 2 -receptor agonist, also scavenges free radicals and suppresses lipid peroxidation. 77) In addition, ropinirole increases the level of the endogenous antioxidant glutathione (GSH) and increases the expression of GSHPx, GSH reductase and GSH S-transferase. 78) In contrast, other non-ergot D 2 -receptor agonists, pramipexole and talipexole, inhibited MPP ϩ -induced ROS production, 25) although it is unknown whether these drugs directly scavenge ROS.…”