Clonidine, dexmedetomidine: alpha-2 adrenergic receptor agonists in neuroscience


  • Jabril B. Eldufani Department of Medicine, University of Montreal, Montreal, Quebec, Canada
  • Nyruz R. Elahmer Department of Pharmacology and Physiology, University of Montreal, Montreal, Quebec, Canada
  • Alireza Nekoui Department of Medicine, University of Montreal, Montreal, Quebec, Canada
  • Gilbert A. Blaise Department of Medicine, University of Montreal, Montreal, Quebec, Canada Department of Anesthesiology and Pain Management, Management, University Hospital of Montreal (CHUM), Montreal, Quebec, Canada



α-2 AR agonists, Cognitive, Depression, Immune system, Pain, Sleep


The alpha-2 adrenergic receptor (α-2 AR) agonists have a long history of use in treating different clinical conditions, such as hypertension, psychiatric entities (e.g., attention-deficit hyperactivity disorder), chronic pain, panic disorders, and, lately, for treating opioid withdrawal syndrome. In recent years, α-2 AR medications have been administered as adjuncts for managing inflammatory conditions, depression, chronic pain, sleep and cognitive disorders. This review will provide some clinical applications in neuroscience for this class of drugs. Understanding the pharmacological mechanisms is essential to obtaining neurochemical data that demonstrate that α-2 AR agonists have potential clinical significance in neuroscience.


Ahlquist RP. A study of the adrenotropic receptors. Am J Physiology-Legacy Content. 1948 Jun 1;153(3):586-600.

Brown BR, Brodsky JB, Bravo JJ. Acute postoperative clonidine withdrawal syndrome. Anesthesiology. 1976 Jun 1;44(6):519.

Barbani F, Angeli E, and De Gaudio AR. (2018). Intravenous Sedatives and Analgesics. In Critical Care Sedation. Springer, Cham;2018:69-101.

Shukry M, Clyde MC, Kalarickal PL, Ramadhyani U. Does dexmedetomidine prevent emergence delirium in children after sevoflurane‐based general anesthesia?. Pediatr Anesthesia. 2005 Dec;15(12):1098-104.

Nikolic K, Agbaba D. Imidazoline antihypertensive drugs: selective i1‐imidazoline receptors activation. Cardiovascular Therapeutics. 2012 Aug;30(4):209-16.

Giovannitti Jr JA, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesthesia Progress. 2015 Mar; 62(1):31-8.

Schmitt H. The pharmacology of clonidine and related products. In Antihypertensive agents. Springer, Berlin, Heidelberg.1977:299-396.

Gazi L, Nickolls SA, Strange PG. Functional coupling of the human dopamine D2 receptor with Gαi1, Gαi2, Gαi3 and Gαo G proteins: evidence for agonist regulation of G protein selectivity. Br J Pharmacol. 2003 Mar 1;138(5):775-86.

Naaz S, Ozair E. Dexmedetomidine in current anaesthesia practice-a review. Journal of clinical and diagnostic research: JCDR. 2014 Oct;8(10):GE01.

Romero-Sandoval A, Eisenach JC. Perineural clonidine reduces mechanical hypersensitivity and cytokine production in established nerve injury. J Am Soc Anesthesiologists. 2006;104(2):351-5.

Zhu YJ, Peng K, Meng XW, Ji FH. Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model. Brain Res. 2016 Aug 1;1644:1-8.

Hall JE, Uhrich TD, Ebert TJ. Sedative, analgesic and cognitive effects of clonidine infusions in humans. Br J Anaesthesia. 2001 Jan 1;86(1):5-11.

Denolle T, Sassano P, Allain H, Bentué‐Ferrer D, Breton S, Cimarosti I, et al. Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients. Fundamental Clin Pharmacol. 2002;16(6):527-35.

Ortega MR, Jambrina CC, Vallhonrat IL, Simón IF. Indications of dexmedetomidine in the current sedoanalgesia trends in the critical patient. Med Intensiva. 2014 Jan 1;38(1):41-8.

Scott-Warren VL, Sebastian J. Dexmedetomidine: its use in intensive care medicine and anaesthesia. BJA Education. 2015 Sep 26;16(7):242-6.

Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, et al. Dexmedetomidine for Long-Term Sedation Investigators: Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: Two randomized controlled trials. JAMA. 2012;307(11):1151-60.

Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F et al. Dexmedetomidine vs. midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301:489-99.

Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell Jr FE, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62.

Wilsey JT, Block JH. Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model. J Pain Research. 2018;11:693.

Pyati S, Gan TJ. Perioperative pain management. CNS Drugs. 2007 Mar 1;21(3):185-211.

Elia N, Culebras X, Mazza C, Schiffer E, Tramèr MR. Clonidine as an adjuvant to intrathecal local anesthetics for surgery: systematic review of randomized trials. Regional Anesthesia Pain Med. 2008 Mar 1;33(2):159-67.

Uhle EI, Becker R, Gatscher S, Bertalanffy H. Continuous intrathecal clonidine administration for the treatment of neuropathic pain. Stereotactic and functional neurosurgery. 2000;75(4):167-75.

Ackerman LL, Follett KA, Rosenquist RW. Long-term outcomes during treatment of chronic pain with intrathecal clonidine or clonidine/opioid combinations. J Pain Symptom Management. 2003 Jul 1;26(1):668-77.

Bekker A, Sturaitis MK. Dexmedetomidine for neurological surgery. Neurosurgery. 2005;57:1-10.

Ghanizadeh A. Insomnia, night terror, and depression related to clonidine in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2008 Dec 1;28(6):725-6.

Antkiewicz-Michaluk L, Romańska I, Wąsik A, Michaluk J. Antidepressant-like effect of the endogenous neuroprotective amine, 1MeTIQ in clonidine-induced depression: behavioral and neurochemical studies in rats. Neurotoxicity Res. 2017 Jul 1;32(1):94-106.

Wijeysundera DN, Bender JS, Beattie WS. Alpha-2 adrenergic agonists for the prevention of cardiac complications among patients undergoing surgery. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD004126.

Aksay SS, Bumb JM, Remennik D, Thiel M, Kranaster L, Sartorius A, Janke C. Dexmedetomidine for the management of postictal agitation after electroconvulsive therapy with s-ketamine anesthesia. Neuropsychiatric Disease Treatment. 2017;13:1389.

Anger KE. Dexmedetomidine: a review of its use for the management of pain, agitation, and delirium in the intensive care unit. Curr Pharm Des. 2013 Jul 1;19(22):4003-13.

Reade MC, Finfer S. Sedation and delirium in the intensive care unit. N Engl J Med. 2014;370(5):444-54

Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 4 ed; 2013.

Sallee F, Connor DF, Newcorn JH. A review of the rationale and clinical utilization of α2-adrenoceptor agonists for the treatment of attention-deficit/hyperactivity and related disorders. J Child Adolescent Psychopharmacol. 2013 Jun 1;23(5):308-19.

Miyazaki S, Uchida S, Mukai J, Nishihara K. Clonidine effects on all‐night human sleep: Opposite action of low‐and medium‐dose clonidine on human NREM–REM sleep proportion. Psychiatry Clin Neurosci. 2004 Apr;58(2):138-44.

Kinzie JD, Sack RL, Riley CM. The polysomnographic effects of clonidine on sleep disorders in posttraumatic stress disorder: a pilot study with Cambodian patients. J Nervous Mental Dis. 1994 Oct.

Morgenthaler TI, Auerbach S, Casey KR, Kristo D, Maganti R, Ramar K, et al. Position paper for the treatment of nightmare disorder in adults: an american academy of sleep medicine position paper. J Clin Sleep Med. 2018 Jun 15;14(06):1041-55.

Kung S, Espinel Z, Lapid M. Treatment of nightmares with prazosin: a systematic review. Mayo Clin Proc. 2012;87(9):890–900

Ming X, Gordon E, Kang N, Wagner GC. Use of clonidine in children with autism spectrum disorders. Brain Develop. 2008 Aug 1;30(7):454-60.

Huupponen E, Maksimow A, Lapinlampi P, Särkelä M, Saastamoinen A, Snapir A, et al. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand. 2008 Feb;52(2):289-94.

Halassa MM, Florian C, Fellin T, Munoz JR, Lee SY, Abel T, et al. Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss. Neuron. 2009 Jan 29;61(2):213-9.

Garrity AG, Botta S, Lazar SB, Swor E, Vanini G, Baghdoyan HA, et al. Dexmedetomidine-induced sedation does not mimic the neurobehavioral phenotypes of sleep in Sprague Dawley rat. Sleep. 2015 Jan 1;38(1):73-84.




How to Cite

Eldufani, J. B., Elahmer, N. R., Nekoui, A., & Blaise, G. A. (2018). Clonidine, dexmedetomidine: alpha-2 adrenergic receptor agonists in neuroscience. International Journal of Basic & Clinical Pharmacology, 7(12), 2476–2482.



Review Articles