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One commonly used premedication is [[clonidine]], an [[Alpha-adrenergic agonist#α2 agonists|alpha-2 adrenergic agonist]].<ref>{{cite journal | vauthors = Bergendahl H, Lönnqvist PA, Eksborg S | title = Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedication | journal = Acta Anaesthesiologica Scandinavica | volume = 50 | issue = 2 | pages = 135–143 | date = February 2006 | pmid = 16430532 | doi = 10.1111/j.1399-6576.2006.00940.x | s2cid = 25797363 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dahmani S, Brasher C, Stany I, Golmard J, Skhiri A, Bruneau B, Nivoche Y, Constant I, Murat I | display-authors = 6 | title = Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies | journal = Acta Anaesthesiologica Scandinavica | volume = 54 | issue = 4 | pages = 397–402 | date = April 2010 | pmid = 20085541 | doi = 10.1111/j.1399-6576.2009.02207.x | s2cid = 205430269 | doi-access = free }}</ref> It reduces postoperative shivering, [[postoperative nausea and vomiting]], and emergence [[delirium]].<ref name=":11" /> However, a randomized controlled trial from 2021 demonstrated that clonidine is less effective at providing anxiolysis and more sedative in children of preschool age. Oral clonidine can take up to 45 minutes to take full effect,<ref>{{Cite journal |last1=Bromfalk |first1=Åsa |last2=Myrberg |first2=Tomi |last3=Walldén |first3=Jakob |last4=Engström |first4=Åsa |last5=Hultin |first5=Magnus |date=November 2021 |editor-last=Cravero |editor-first=Joseph |title=Preoperative anxiety in preschool children: A randomized clinical trial comparing midazolam, clonidine, and dexmedetomidine |journal=Pediatric Anesthesia |language=en |volume=31 |issue=11 |pages=1225–1233 |doi=10.1111/pan.14279 |pmid=34403548 |s2cid=237197251 |issn=1155-5645|doi-access=free }}</ref> The drawbacks of clonidine include [[hypotension]] and [[bradycardia]], but these can be advantageous in patients with hypertension and tachycardia.<ref>{{cite journal | vauthors = Henry RG, Raybould TP, Romond K, Kouzoukas DE, Challman SD | title = Clonidine as a preoperative sedative | journal = Special Care in Dentistry | volume = 38 | issue = 2 | pages = 80–88 | date = March 2018 | pmid = 29364538 | doi = 10.1111/scd.12269 | s2cid = 3875130 }}</ref> Another commonly used alpha-2 adrenergic agonist is dexmedetomidine, which is commonly used to provide a short term sedative effect (<24 hours). [[Dexmedetomidine]] and certain [[atypical antipsychotic]] agents may be also used in uncooperative children.<ref>{{Cite journal |last1=Manning |first1=Alexander N. |last2=Bezzo |first2=Leah K. |last3=Hobson |first3=Jamie K. |last4=Zoeller |first4=Justine E. |last5=Brown |first5=Courtney A. |last6=Henderson |first6=Kristin J. |date=October 2020 |title=Dexmedetomidine Dosing to Prevent Pediatric Emergence Delirium |url=https://pubmed.ncbi.nlm.nih.gov/32990204 |journal=AANA Journal |volume=88 |issue=5 |pages=359–364 |issn=2162-5239 |pmid=32990204}}</ref>
Benzodiazepines are the most commonly used class of drugs for premedication. The most commonly utilized benzodiazepine is [[Midazolam]], which is characterized by a rapid onset and short duration. Midazolam is effective in reducing [[Preoperational anxiety|preoperative anxiety]], including [[Separation anxiety disorder|separation anxiety]] in children.<ref>{{Cite journal |last=El Batawi |first=Hisham Yehia |date=2015 |title=Effect of preoperative oral midazolam sedation on separation anxiety and emergence delirium among children undergoing dental treatment under general anesthesia |journal=Journal of International Society of Preventive & Community Dentistry |volume=5 |issue=2 |pages=88–94 |doi=10.4103/2231-0762.155728 |issn=2231-0762 |pmc=4415335 |pmid=25992332 |doi-access=free }}</ref> It also provides mild sedation, [[sympathicolysis]], and [[anterograde amnesia]].<ref name=":11" />
[[Melatonin]] has been found to be effective as an anaesthetic premedication in both adults and children because of its [[hypnotic]], [[anxiolytic]], [[Sedation|sedative]], [[Nociception|analgesic]], and [[anticonvulsant]] properties. Recovery is more rapid after premedication with melatonin than with midazolam, and there is also a reduced incidence of post-operative [[Psychomotor agitation|agitation]] and delirium.<ref name="Naguib2007">{{cite journal | vauthors = Naguib M, Gottumukkala V, Goldstein PA | title = Melatonin and anesthesia: a clinical perspective | journal = Journal of Pineal Research | volume = 42 | issue = 1 | pages = 12–21 | date = January 2007 | pmid = 17198534 | doi = 10.1111/j.1600-079X.2006.00384.x | doi-access = free }}</ref> Melatonin has been shown to have a similar effect in reducing perioperative anxiety in adult patients compared to benzodiazepine.<ref>{{cite journal | vauthors = Madsen BK, Zetner D, Møller AM, Rosenberg J | title = Melatonin for preoperative and postoperative anxiety in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD009861 | date = December 2020 | issue = 12 | pmid = 33319916 | pmc = 8092422 | doi = 10.1002/14651858.CD009861.pub3 }}</ref>
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