Difference between monoamine transport inhibitor and substrate?

[ecstacylover]

I know that monoamine transporter inhibitors work by having a higher affinity for the transporter than the endogenous ligand, thus blocking it from being bound and uptaken.

A substrate would basically do the same, but I understand that it is also transported into the cytoplasm in the manner of the endogenous ligand.

I would assume that not all inhibitors are substrates, due to steric hindrance, etc., but are there any reliable methods of determining this? If anyone has any good sources I'd be interested.

The main reason I'm interested is because some receptors are intracellular, so the drug must either be transported into the cell or diffuse across the membrane to interact with them.

 

[sekio]

Transport inhibitors bind to the site that the substrate would, but don't change the conformation of the protein "enough" to transport the chemical in question across the membrane.

As far as I know monoamine transporters are pretty selective, the substrates tend to be the three/four monoamines (dopamine, norepinephrine, epinephrine/adrenaline, serotonin).

Also, intracellular/nuclear receptors tend not to be the "fun" sort, c.f. glucocorticoid receptor, aryl hydrocarbon receptor, etc.

 

[ecstacylover]

Okay thanks. The main intracellular receptor I'm interested in is TAAR1 which plays a role in monoamine release. So I would expect any drug which evokes monoamine release to be a transporter substrate if it cannot diffuse across the membrane. For example, amphetamine is a substrate at the DAT.