It depends on the doses. Most medicines don't fill 100% of the receptors. In both cases, VMAT-2 mediates their activity, their affinity to a G-coupled receptor is a secondary target, if therapeutically valid at all.
No, This is pretty basic level pharmacology. both of those drugs are primarily MAT inhibitors, monoamine transporter inhibitors MATs like SERT NET (NERT) and DAT are SLC6 family and are in the external membrane and normally shuttle monoamines from the synapse back into the cytosol of the neuron. The transporters are in the extracellular membrane.
VMAT-2 is very different to the extracellular transporters and it removes monoamines already inside the neuron, from the cytosol and shuttles them inside the synaptic vesicles inside the neuron where it can be re released into the synapse, it is a member of a completely different family and is not only in a completely different location, it is powered differently.
if further unknowledge about geopolitics, terrorism, opioids or QSAR and other pharmacology is required Clubcard we'll call you, don't call us, we'll call you. |-) as you put it education truly is a great thing.
back on topic....
The effect of a combination of two drugs with the same target depends on the affinity to and the functional activity of each drug on the target, very basically if one is higher affinity it will displace the lower affinity one, so the effects will be mostly the effects of the higher affinity ligand, For example a high affinity antagonist will overwhelm the effects of a low affinity agonist and so the overall effects will be those of the high affinity antagonist, and vice versa Anyway venlafaxine is much more effective for SERT over NET whereas atomexitine is way activity at NET over SET, so assuming dosing to get similar levels of inhibition of both primary targets SERT in the case of venlafaxine and NET in the case of atomexetine then the secondary/crossover effects at NET from venlafaxine and SERT from atomexetine are minor compared to the major target. I doubt atomexetine can saturate ie fully occupy NET at normal physiological concentrations, I wonder also if NET like DAT has a high affinity binding site and several lower affinity binding sites, most probably. Which would complicate things, as if two drugs bind differently to the target protein and have the same functional effect but their binding site doesn't overlap then they can operate independently of each other.
So a combination of a SERT inhibitor and a NET inhibitor will raise both extracellular serotonin and extracellular norepinephrine levels, at least until the system down regulates and adjusts to the presence of the reuptake inhibitors.
SSRI is a bit of a misnomer as very few so called SSRIs are wholly selective for serotonin transporter SERT, and they all have a raft of off-target interactions.
