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Dexmedetomidine for ADHD


Dexmedetomidine for ADHD

Dexmedetomidine is a potent selective α2-adrenoreceptor agonist.

The binding of dexmedetomidine to α2 receptors is 1620 times stronger than to α1 receptors. For comparison: clonidine 220:1.
The affinity for α2 receptors for dexmedetomidine is higher than that for clonidine.1

α2-Agonists (such as clonidine and guanfacine) are used as 3rd choice ADHD medications.23

mediate α2 receptors:1

  • Inhibition of presynaptic noradrenaline release
  • Central induction of sedation via the nucleus coeruleus
  • Central moderation of pain perception via the dorsal posterior horn
  • Inhibition of insulin secretion from pancreatic beta cells

All 3 subtypes of α2 receptors inhibit adenylyl cyclase. This reduces cyclic adenosine monophosphate and causes hyperpolarization of noradrenergic neurons in the medial dorsal pons, particularly in the locus coeruleus.4 When cyclic adenosine monophosphate is inhibited, potassium efflux through calcium-activated channels prevents calcium ions from entering the nerve terminal, which suppresses neuronal firing. This suppression inhibits the release of noradrenaline and decreases the activity of ascending noradrenergic signaling pathways, leading to hypnosis and sedation.5 This negative feedback loop can further reduce heart rate, blood pressure and sympathetic stress response.1

Dexmedetomidine is widely used for sedation and anesthesia in clinical perioperative applications.6

Dexmedetomidine activates dopaminergic neurons in the VTA.7

Intravenous administration of dexmedetomidine below the usual sedative dose (and without sedative effect) reduced hyperactivity and improved spatial working memory in SHR, a model animal for ADHD.8
The use of dexmedetomidine in people with ADHD is not yet known.

  1. Giovannitti JA Jr, Thoms SM, Crawford JJ (2015): Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015 Spring;62(1):31-9. doi: 10.2344/0003-3006-62.1.31. PMID: 25849473; PMCID: PMC4389556. REVIEW

  2. Harstad E, Shults J, Barbaresi W, Bax A, Cacia J, Deavenport-Saman A, Friedman S, LaRosa A, Loe IM, Mittal S, Tulio S, Vanderbilt D, Blum NJ (2021): α2-Adrenergic Agonists or Stimulants for Preschool-Age Children With Attention-Deficit/Hyperactivity Disorder. JAMA. 2021 May 25;325(20):2067-2075. doi: 10.1001/jama.2021.6118. Erratum in: JAMA. 2021 Oct 12;326(14):1440. PMID: 33946100; PMCID: PMC8097628.

  3. Wilens TE, Robertson B, Sikirica V, Harper L, Young JL, Bloomfield R, Lyne A, Rynkowski G, Cutler AJ (2015): A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Nov;54(11):916-25.e2. doi: 10.1016/j.jaac.2015.08.016. Epub 2015 Sep 15. PMID: 26506582.

  4. Pichot C, Ghignone M, Quintin L (2012): Dexmedetomidine and clonidine: from second- to first-line sedative agents in the critical care setting? J Intensive Care Med. 2012 Jul-Aug;27(4):219-37. doi: 10.1177/0885066610396815. PMID: 21525113. REVIEW

  5. Carollo DS, Nossaman BD, Ramadhyani U (2008): Dexmedetomidine: a review of clinical applications. Curr Opin Anaesthesiol. 2008 Aug;21(4):457-61. doi: 10.1097/ACO.0b013e328305e3ef. PMID: 18660652. REVIEW

  6. Bong CL, Tan J, Lim S, Low Y, Sim SW, Rajadurai VS, Khoo PC, Allen J, Meaney M, Koh WP (2019): Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants. Br J Anaesth. 2019 May;122(5):662-670. doi: 10.1016/j.bja.2018.12.027. PMID: 30916007.

  7. Qiu G, Wu Y, Yang Z, Li L, Zhu X, Wang Y, Sun W, Dong H, Li Y, Hu J (2020): Dexmedetomidine Activation of Dopamine Neurons in the Ventral Tegmental Area Attenuates the Depth of Sedation in Mice. Anesthesiology. 2020 Aug;133(2):377-392. doi: 10.1097/ALN.0000000000003347. PMID: 32412932.

  8. Xu X, Zhuo L, Zhang L, Peng H, Lyu Y, Sun H, Zhai Y, Luo D, Wang X, Li X, Li L, Zhang Y, Ma X, Wang Q, Li Y (2023): Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation. Psychiatry Res. 2023 May;323:115172. doi: 10.1016/j.psychres.2023.115172. PMID: 36958092.

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