I was wondering for a while, whether or not blood brain barrier (BBB) is truly "impenetrable" by neurotransmitter. Although it's true that neurotransmitter such as dopamine cannot penetrate BBB on it's own, I do wonder whether or not the concentration inside the brain is truly unrelated to the concentration in the blood. If I ask around, it seems to be the consensus that the two are working completely independently. Still, there has been multiple (although not many) research that mentions that urinary dopamine might also reflect the severity of the symptom. How is it so?

I would like to argue that even if two people are separated by a solid door, they can still communicate if voices or notes can pass through the gaps.

Similarly, even if dopamine itself cannot pass through, antipsychotics and precursor of dopamine can pass. Antipsychotics cannot specifically work on the brain, so if there is a large amount of dopaminergic activity along the way, antipsychotic may be exhausted to block the receptors along the way. Basically, increase of dopaminergic activity in the peripheral tissue may lessen effectiveness of antipsychotics. As antipsychotics cannot alter production of dopamine, leakage of dopamine to blood or urine might reflect mis-targetted receptors. With such logic, maybe usage of domperidone may increase the capability of other antipsychotics to work on the brain, even when domperidone cannot pass the BBB.

The similar mechanism can be deduced about precursors of neurotransmitter. If we're assuming that the precursors move based on their own concentration gradient, then it's possible that they actually move toward the area with more neurotransmitter activity and decreases in area with less activity. In this way, increased dopamine production in the brain can decrease dopamine production in the peripheral tissues and blockade of brain dopamine production via presynaptic dopamine receptor may increase dopamine in peripheral tissue.

Although this is just a question out of curiosity and there isn't much research on this issue, what do you think about it?