Posted by SLS on January 6, 2001, at 9:04:24
In reply to Re: Pindolol+Busirone+neuroleptic safe? For Andrew, posted by anita on January 5, 2001, at 23:07:12
> Can you please tell me where you saw that low-dose Zyprexa is a D2 autoreceptor antagonist? I have been looking for this info for ages. Do you know if low-dose risperidone is as well?
From the bowels of my mind, I seem to have vague memories of things that I can't verify right now. I think most, if not all neuroleptic D2 receptor antagonists block both presynaptic and postsynaptic receptors simultaneously. The differences seem to lie in their relative affinities for both types of receptor. I believe they have variances in specific domains. In addition, D2 receptors exist in low-affinity and high-affinity states. Sulpiride and amisulpride are considered "preferential" for D2 presynaptic autoreceptors relative to postsynaptic D2 receptors; it binds more tightly to pre- than post-. The molecular configurations (conformations?) of presynaptic and postsynaptic receptors are generally different enough to actually differ in their affinities for endogenous dopamine and other ligands. Presynaptic autoreceptors are of significantly higher affinity, or more generally in the high-affinity state. Therefore, some D2 ligands will bind more tightly and occupy first presynaptic autoreceptors as the concentration increases where the number of postsynaptic receptors blocked becomes clinically significant. My guess is that some ligands actually cause the receptor to change conformations from one state to the other. Perhaps amisulpride switches and locks presynaptic autoreceptors into their high-level affinity state, making them less likely to be displaced by dopamine while being incapable of switching and locking the molecularly different postsynaptic receptors. My guess is that nonpreferential neuroleptics with low binding affinities to D2 receptors (Risperdal and Zyprexa) would foster a greater pre/post ratio of antagonism at low dosages, thus producing enhanced dopaminergic transmission in limbic and and other structures involved with mood (Anita knows better what structures are involved).
- Scott
poster:SLS
thread:50944
URL: http://www.dr-bob.org/babble/20001231/msgs/51024.html