Lower heart rate on stimulant, during exercise?

[checktest]

Just thought I would see about some thoughts. Over the past month I've resumed taking methylphenidate, and I've noticed having lower HR when doing some cardio relative to what it normally is. Gym got some new stair machines, and while I
usually average 166-174 for a decent period, I've been closer to 154-162 in the evening ~6 after taking the ritalin ER at noon or 11. Same routine/steadily increasing difficulty. I don't mean over the month, but even one day vs. the next.

Just trying to figure it out. I was guessing maybe less caffeine on ritalin days, but my caffeine is pretty constant and not high. Then maybe something with the sensors not detecting heartrate as well (need to get a new heart monitor, using the equipment), but it feels less, and is less on palpation. Some odd vasoconstriction or reactive vasodilation thing. Maybe something about the timing, some sort of 'comedown' of heart rate, though I certainly don't feel a 'comedown' and do the same.

I noticed this before when I was on parnate and ritalin, but I chalked that up to upping my BP and reducing the reactive HR due to postural hypotension, or something like that.

Currently on a little bit of an odd cocktail. 60 mg mirtazapine, 15 mg vortioxetine, 112.5 bupropion, and 10 mg methylphenidate ER. I've had some ekgs and checked my BP ~110/70 average say, so nothing seems to be awry in average conditions.. More relaxed and balanced, little less anxious on the methylphenidate. I don't have ADD, just dep/anx. Actually feeling pretty normal.

As for less obvious drug interactions I know vortioxetine has some B1 activity/antagonism and there could be some weird interplay, but I didn't notice this on 150 of bupropion...which does increase the levels of vortioxetine. Uncertain about Mirt adrenoceptor balance.

Perhaps alpha2 agonism by methylphenidate is predominant in this case (opp. Mirt), which would make sense in the light of guanfacine clonidine actions. https://www.nature.com/articles/1300818

 

[CFC]

I don't think I can give you a definitive answer, but what you're experiencing is pretty common. It's not to do with postural hypotension - that's an acute thing that occurs in the transition from lying or sitting to standing. When you're exercising you're long past that stage. And I think it's unlikely to be pre-synaptic alpha-2 agonism in the heart either.

Rather, increased alpha-1 agonism in the myocardium (from MPH) should raise contractile force, which improves the heart's efficiency (and sometimes but not always BP) without increasing HR. And a more efficient heart doesn't need to beat as fast to supply the muscles with adequate oxygenated blood during intense exercise. Meanwhile the effect of alpha-1 vasoconstriction at the periphery and around organs tends to increase the supply of blood to the muscles, heart and lungs, improving arterial blood flow there and oxygen exchange in the lungs and so further reducing peak HR during cardio.

Having said that, it's all highly dependent on the various ratios of beta to alpha agonism (and the 10+ receptor subtypes, and calcium channels etc) at different sites in the body. This is why stimulants affect people differently. And this would be particularly true in a case like yours when taking a cocktail of drugs which all have contradictory or additive effects. Which is why GPs are usually forced to measure changes in BP and HR in vivo when adding/subtracting a drug, as that change can't be reliably predicted beforehand.

Not sure how up you are on all this, so here's some reading that you might find helpful to try and understand what's going on and the various mechanisms.

 

[checktest]

Fantastic! Thanks for the link and the clear line of reasoning. I've been much too focused on monoaminergic and some diabetic drug pathways [glp1 mimetics weight loss, dpp4 inhibitors fibrosis.] Meaning to read up on adrenergic. And whatever sigma nonsense really is, at least they crystallized the receptor, TM ER proteins ain't easy.

Yes, treatment becomes much more empirical and reactionary with polypharmacy. We don't have the understanding and the systems are complex. Would be a great model to work on, adrenergic control with pumps, flow, vessel resistance. Control layer and sensors, baroreceptors.

The postural hypotension was not transitory on parnate, haha. Always 90s and lower sys BP on standing for the entire period, HR 90s and up. Compression stockings were good. Octopamine replacement or whatever other theories. Thanks again!