Posted by Astounder on November 15, 2007, at 19:25:05
In reply to Re: Numanda for Adderall/Dex tolerance? » Astounder, posted by Questionmark on November 11, 2007, at 23:23:24
> How likely do you think that the reason amantadine has been shown to upregulate D2 receptors is that it has some D2 agonist properties (although it's supposed to be a dopamine releaser from what i understand) and consequently causes an upregulation of D2 receptors? Why or why not?
> Thanks.The specific dopaminergic action of amantadine is not well characterized. It is referred to as a DRI, but I can't find binding data. NMDAR inhibition is 10-fold less potent than memantine, and it's action is voltage-dependant (unlike DXM and other dissociatives). Amantadine is probably a ligand like memantine is for nicotinic acetylcholine receptors, which modulate DA release.
The upregulation of postsynaptic D2 receptors is probably do to either uncompetetive NMDAR blockade and (if a ligand) nAChR blockade. Preventing excessive burst firing of DA neurons while increasing tone through DAT blockade probably accounts for its effects on reducing/preventing L-DOPA-induced dyskinesia. Note that Parkinson's patients have very low DAT levels, probably an adaptive change, so DAT blockade alone is not sufficient to explain its actions in these persons.
Normal NE/DAergic drugs, the psychostimulants, all cause postsynaptic D2 downregulation. However, they also cause rapid change in DAT expression. Amphetamines decrease DAT expression--less places for it to release DA from--while cocaine, Wellbutrin, and probably methylphenidate increase DAT expression--harder to plug all the uptake pumps. It may be actions at DAT itself that attenuates tolerance rather than the postsynaptic site. DAT expression is going to play a much larger role in people with intact DA terminals than those with Parkinsons.
poster:Astounder
thread:792510
URL: http://www.dr-bob.org/babble/20071115/msgs/795336.html