Posted by linkadge on October 31, 2007, at 22:36:42
In reply to Re: Dopamine agonists cause sedation. But why??, posted by Astounder on October 31, 2007, at 14:02:28
>.) Unlike DA, DA agonists always have a higher >affinity for D2Sh than D2Lh. D2Lh is the >postsynaptic receptor that mediates the >reinforcing, mood elevating, psychomotor >activating, wakefulness promoting, and >psychotomimetic effects of the psychostimulants >we all know and love. D2Sh is the inhibitory >presynaptic autoreceptor; activation of this >inhibits exocytotic release of dopamine from the >axon terminal into the synaptic cleft.
But does it make sense that the theraputic effect of a dopamine agonist would correspond with an overal decrease in post synaptic receptor stimulation?
If they do have higher affinity for presynaptic autoreceptors and the sedation does correspond to a decrease in dopamine release, then why would one get improvement in Parkinson's symptoms right after dosing? Wouldn't one expect the net decrease in post synaptic dopamine receptor function to correspond to worsening Parkinsonian symptoms?
So I guess what I am saying is why do parkinsons symptoms remit at the same time as an increase in sedation? You obviously are getting a net increase in dopaminergic neurotransmission at this point or else or else parkinsons symptoms wouldn't decrease, yet you are experiencing somnolence at the same time.
Also, one would expect the autoreceptors would desensize leading to a net increase in dopamine release overtime. Does the sedation improve over time (I don't know I have never taken it)
Linkadge
poster:linkadge
thread:791344
URL: http://www.dr-bob.org/babble/20071027/msgs/792666.html