Posted by Questionmark on November 18, 2004, at 14:45:48
In reply to Re: What do you think of Parnate + amisulpride? » Chairman_MAO, posted by SLS on November 12, 2004, at 7:56:07
What a great idea-- adding amisulpride or another D2 antagonist to a D2 agonist to counter the lethargy. And what a smart way to help determine if that would work-- looking at the respective binding affinities of those three drugs on the D2 receptor. You guys are brilliant.
Anyway, are there autoreceptors of DA other than D2? If not, or not to a strong degree, then why aren't there dopamine agonists that just bind to D1 and/or D3 and/or D4 receptors? (Are there D1 autoreceptors?)
Oh and by the way, i've been wondering for quite some time now why D2 agonists are capable of causing such drowsiness and lethargy, and now i know why. So thank you. It eases some confusion that i had.
> Hi CM.
> > Have you considered trying parnate + amisulpride?
> Not really, although it's a good thought. In the past, I have tried adding Risperdal and Zyprexa to a combination of Parnate + desipramine. My reactions were the same. I experienced a significant (25% improvement) antidepressant within the first few days that lasted for 5 days or so.
> > Or Parnate + amisulpride + memantine/lamictal/other NMDA antagonist?
> If I do try adding amisulpride, I will definitely be taking Lamictal 300mg.
> > I've also been wondering about whether amisulpride would prevent DA agonists from eventually causing lethargy by preventing them from stimulating the autoreceptors.
> Isn't that something how consistently Mirapex produces a latent lethargy? I guess something is happening presynaptically, as this phenomenon looks similar to low-dose apomorphine-induced sedation. I think the success of your strategy would depend upon the relative affinities of the two drugs for the receptor. Amisulpride is an extremely potent ligand for the presynaptic receptor, much more so than sulpiride. I don't know how it compares to the various agonists, though. One would like amisulpride to be a stronger ligand than the agonist. The following values that I found on the Internet represent the affinity of ligand for the D2 receptor. However, it doesn't diffentiate between presynaptic versus postsynaptic affinities. Presynaptic receptors are of substantially higher binding affinity than postsynaptic. If we assume that the ligands bind to both pre- and post- synaptic receptors in the same relative order of affinity, then your strategy might work.
> K(i) for D2
> amisulpride 1.3 - 3.8 nM
> pramepexole 750 - 1500 nM
> ropinerole 650 - 1000 nM
> I appreciate your input.
> - Scott