Dosing two monoamine/catecholamine drugs at the same time?

[JohnBoy2000]

Is this bad mmkay?

I know some people dose say, a GABA agent, and a monoamine agent simultaneously.

What I had been doing was, taking an alpha 2 adrenergic blocker at night, then a much smaller dose in the morning additionally, at the same time as taking an NRI.
I think it might be having a counter productive effect.

Now - there are no P450 CYP interactions between the drugs.

P-glycoprotein - I don't know but, when taken 12 hours apart, they definitely don't interact.
Do p-glycoprotein interactions persist for as long as CYP? i.e. up to a week from the dose of the interacting drug?
Or can they abait in the space of hours?

Can they interact, when taken, closer together?

When I was taking desipramine (lofepramine), I once dosed the lot at one time, and it had a similar fatigue inducing effect.
Though, when the dosing was spaced out - it was fine.

What exactly is the mechanism behind that?
Maybe, just too much NA at one time?

Is there an explanation for it?

 

[Cotcha Yankinov]

I think upregulation of efflux pumps like p-gp is more of a chronic thing resulting in pharmacokinetic tolerance, I'm not sure quite how acute it is or if the pumps can be effectively saturated when combining meds

I'm under the impression that the 3 major NE receptor subtypes (a1, a2 and b2) have kind of a dosage dependent role, with different subtypes playing more or less of a role with more or less NE, and at some point subtypes that mediate fatigue may override other subtypes. That kind of biphasic effect is common I suppose.

NE can certainly lead to inhibition.

As far as a counterproductive effect, normally NRI in the PFC should lead to increased NE binding postsynaptically (a2) but mirtazapine could reduce the post-synaptic binding at some point, even if it increased presynaptic release by blocking autoreceptors. I suppose if the autoreceptors were already desensitized then mirtazapine would tend to block the post synaptic response moreso than facilitate presynaptic release.