The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 8 • December 2015

Alpha2 Adrenergic Agonists May Mimic Recovery Sleep

After not getting enough sleep, recovery sleep is an induced state that helps restore normal waking feeling and behavior. A paper (Zhang, 2015) reports that, “...recovery sleep and alpha 2 adrenergic receptor-induced sedation were not only similar behavioral states, but were both induced by activating similar neuronal populations in the PO [preoptic] hypothalamus.” The researchers found that GABAergic neurons in the LPO (preoptic hypothalamus) were required for the onset of dexmedetomidine-induced sedation. Desmedetomidine is an alpha2 adrenergic agonist used in clinical practice as an anesthetic.

This might be useful for people who have lost sleep and want to try using an alpha2 adrenergic receptor agonist to help them recover. Clonidine is such an agonist, a prescription drug that has been widely used as a sedative and is safe for most normal people at usual dosage prescribed. It will put you to sleep, so don’t take it when you plan to be working or driving. This drug may help relieve restless legs, but in Sandy’s experience it helped only when taken at night before bedtime. Natural products that act as agonists at alpha 2 adrenergic receptors are arginine and possibly agmatine (decarboxylated arginine found naturally in human serum) (Joshi, 2007). Clonidine potently lowers blood pressure, so be very cautious about dizziness-induced falls.

Interestingly, the authors (Zhang, 2015) note that, “candidate homeostat molecules, which accumulate proportionally to the amount of sleep deprivation and act locally in the preoptic area, include PGD2 [prostaglandin D2] and adenosine.” PGD2 is released in a pulse by immediate release niacin at doses of 50 mg or more, depending on individual sensitivity. We have found niacin to have a calming, sometimes nap-inducing effect.


  • Zhang, Ferretti, Guntan, et al. Neuronal ensembles sufficient for recovery sleep and the sedative action of alpha2 adrenergic agonists. Nat Neurosci. 18(4):553-61 (2015).
  • Joshi, Ferguson, Johnson, et al. Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells. Proc Natl Acad Sci U S A. 104(24):9982-7 (2007).

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