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Dopamine Agonists and Lethargy

dopamine

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#1 sub7

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Posted 16 August 2015 - 08:11 AM


Some of the older generation dopamine agonists such as cabergoline are known to make people lethargic and sleepy. In fact some have expressed the side effect as "I feel like sleeping all the time but when i do sleep it is low quality and not refreshing "

I think inserts of these drugs warn about this effect also, as in
"Sleepiness, drowsiness, or sedation is sometimes a significant side effect of certain dopamine agonists, and may interfere with driving or other activities. "
From http://pdcenter.neur...pamine-agonists

Can someone pls explain the mechanism behind this? What I find confusing is that dopamine itself is never associated with such effects and is the cause of alertness and energy- at pretty much any dose. So how come its agonists cause the opposite effect?

#2 gamesguru

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Posted 17 August 2015 - 12:40 PM

I feel like sleeping all the time but when i do sleep it is low quality and not refreshing

I have felt the same from Bacopa, which is a D2 antagonist like haloperidol [1].  Others report a similar paradoxical drowsiness and wakefulness from haliperidol.

 

Agonists/antagonists mess with activity, both in the short- and long-term.  Agonists induce receptor downregulation and reduced activity (especially upon cessation/withdrawal), antagonists induce upregulation and increased activity (especially upon cessation/withdrawal). 

My best explanation then, is that disrupting activity disrupts natural sleep&wake cycles.

Remember in the short-term agonists will increase activity, and after a few weeks or so, then the receptor downregulation starts to compensate and try to re-normalize activity levels.  So in the short-term, it resembles long-term antagonist effects, and visa versa.  Basically it will reduce overall sleep, increase waking frequencies, and as a byproduct, increase drowsiness/fatigue/the feeling of sedation.

 

The roles of dopamine in regulating sleep and waking

Systemic administration of the selective DA D(1) receptor agonist SKF 38393 induces behavioural arousal together with an increase of waking and a reduction of sleep.

On the other hand, injection of a DA D(2) receptor agonist (apomorphine, bromocriptine, quinpirole) gives rise to biphasic effects, such that low doses reduce waking and augment slow-wave-sleep and REMS whereas large doses induce the opposite effects. Not much is known about dopamine-serotonin interaction in the regulation of sleep and waking

 


Edited by gamesguru, 17 August 2015 - 12:45 PM.


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#3 sub7

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Posted 18 August 2015 - 06:20 AM

Thanks a lot for the input
Anyone else?





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