Posted by SLS on May 23, 2008, at 16:21:27
In reply to Re: Sulpiride and Abilify questions..., posted by undopaminergic on May 23, 2008, at 16:11:02
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> > > Postsynaptic agonists overule presynaptic agonists because they directly stimulate postsynaptic receptors regardless of the decrease in DA synthesis and release.
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> > That is dose dependent. At low doses of sulpiride/amisulpride and dopamine direct agonists, the presynaptic effects predominate.
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> Furthermore, with the possible exception of some ergot-based dopamine agonists, they don't stimulate D1-receptors even at high concentrations, and hence fail to make up for the deleterious effects of reduced synthesis and release of endogenous DA. Insufficient (or excessive) stimulation of D1-receptors disturbs working memory, among other things. Fortunately in the case of aripiprazole, antagonism of serotonin 5-HT2A and 5-HT2C antagonism may possibly mitigate this problem.
Why is D1 so important to mood illnesses? I should think that D2 and D3 are more important, as they facilitate the activities of limbic structures, primarily, the nucleus accumbens. Reward, motivation, and all of that stuff. Apomorphine, an unselective DA receptor agonist (including D1), does not appear to have antidepressant properties.The key might not be which DA receptors are affected, but in what tracts they are affected.
- Scott
poster:SLS
thread:829749
URL: http://www.dr-bob.org/babble/neuro/20080418/msgs/830747.html