Editing Pethidine (section)

==Mechanism of action==
{{Main|Opioid}}

Like [[morphine]], pethidine exerts its analgesic effects by acting as an [[agonist]] at the [[μ-opioid receptor]].<ref>{{cite book| vauthors = Bryant B, Knights K |title=Pharmacology for Health Professionals | edition = 3rd |publisher=Mosby Australia|year=2010|location=Chatswood|isbn=978-0-7295-3929-6}}</ref>

Pethidine is often employed in the treatment of postanesthetic shivering. The pharmacologic mechanism of this antishivering effect is not fully understood,<ref name=ISMP2005>{{cite journal | vauthors = Koczmara C, Perri D, Hyland S, Rousseaux L | title = Meperidine (Demerol) safety issues | journal = Dynamics | volume = 16 | issue = 1 | pages = 8–12 | year = 2005 | pmid = 15835452 | url = http://www.ismp-canada.org/download/caccn/CACCN-Spring05.pdf | access-date = 2014-01-11 }}</ref> but it may involve the stimulation of [[κ-opioid receptor]]s.<ref name="Goodman and Gilman">{{cite book| vauthors = Laurence B |title=Goodman & Gilman's pharmacological basis of therapeutics|year=2010|publisher=McGraw-Hill|isbn=978-0071624428|edition=12th|page=549}}</ref>

Pethidine has structural similarities to [[atropine]] and other [[tropane alkaloid]]s and may have some of their effects and side effects.<ref>{{Cite web|url=http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=19741206000040&DocTypeID=3&UserTypeID=0|title = Petidin Meda - FASS Vårdpersonal}}</ref> In addition to these opioidergic and anticholinergic effects, it has [[local anesthetic]] activity related to its interactions with [[sodium ion channel]]s.

Pethidine's apparent ''[[in vitro]]'' efficacy as an antispasmodic agent is due to its local anesthetic effects. It does not have antispasmodic effects ''[[in vivo]]''.<ref>{{cite journal | vauthors = Wagner LE, Eaton M, Sabnis SS, Gingrich KJ | title = Meperidine and lidocaine block of recombinant voltage-dependent Na+ channels: evidence that meperidine is a local anesthetic | journal = Anesthesiology | volume = 91 | issue = 5 | pages = 1481–1490 | date = November 1999 | pmid = 10551601 | doi = 10.1097/00000542-199911000-00042 | s2cid = 34806974 | doi-access = free }}</ref> Pethidine also has stimulant effects mediated by its inhibition of the [[dopamine transporter]] (DAT) and [[norepinephrine transporter]] (NET). Pethidine will substitute for cocaine in animals trained to discriminate cocaine from saline, probably as a result of its inhibitory actions on DAT and NET.<ref name="izenwasser">{{cite journal | vauthors = Izenwasser S, Newman AH, Cox BM, Katz JL | title = The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter | journal = European Journal of Pharmacology | volume = 297 | issue = 1–2 | pages = 9–17 | date = February 1996 | pmid = 8851160 | doi = 10.1016/0014-2999(95)00696-6 }}</ref>

Several [[structural analog|analogs]] of pethidine such as [[4-Fluoropethidine|4-fluoropethidine]] have been synthesized that are potent inhibitors of the reuptake of the [[monoamine neurotransmitter]]s dopamine and [[norepinephrine]] via DAT and NET.<ref>{{cite journal | vauthors = Lomenzo SA, Rhoden JB, Izenwasser S, Wade D, Kopajtic T, Katz JL, Trudell ML | title = Synthesis and biological evaluation of meperidine analogues at monoamine transporters | journal = Journal of Medicinal Chemistry | volume = 48 | issue = 5 | pages = 1336–1343 | date = March 2005 | pmid = 15743177 | doi = 10.1021/jm0401614 }}</ref><ref name="psrs">{{citation | title = Demerol: Is It the Best Analgesic? | journal = Pennsylvania Patient Safety Reporting Service Patient Safety Advisory | volume = 3 | issue = 2 | date = June 2006 | url = http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2006/Jun3(2)/documents/18.pdf | access-date = 2013-04-15 | url-status = dead | archive-url = https://web.archive.org/web/20130620131908/http://patientsafetyauthority.org/ADVISORIES/AdvisoryLibrary/2006/Jun3(2)/documents/18.pdf | archive-date = 2013-06-20 }}</ref> It has also been associated with cases of [[serotonin syndrome]], suggesting some interaction with [[Serotonin|serotonergic neurons]], but the relationship has not been definitively demonstrated.<ref name="izenwasser"/><ref name="psrs"/><ref name="nsw">{{cite web|url=http://www.clininfo.health.nsw.gov.au/nswtag/publications/posstats/Pethidinefinal.pdf|title=Use of pethidine for pain management in the emergency department: a position statement of the NSW Therapeutic Advisory Group|access-date=2007-01-17| vauthors = Davis S |date=August 2004|publisher=New South Wales Therapeutic Advisory Group|url-status=dead|archive-url=https://web.archive.org/web/20061009172524/http://www.clininfo.health.nsw.gov.au/nswtag/publications/posstats/Pethidinefinal.pdf|archive-date=2006-10-09}}</ref><ref name = "Latta">{{cite journal | vauthors = Latta KS, Ginsberg B, Barkin RL | title = Meperidine: a critical review | journal = American Journal of Therapeutics | volume = 9 | issue = 1 | pages = 53–68 | date = January–February 2002 | pmid = 11782820 | doi = 10.1097/00045391-200201000-00010 | s2cid = 23410891 }}</ref>

It is more lipid-soluble than morphine, resulting in a faster onset of action. Its duration of clinical effect is 120–150 minutes, although it is typically administered at 4– to 6-hour intervals. Pethidine has been shown to be less effective than morphine, [[diamorphine]], or [[hydromorphone]] at easing severe pain, or pain associated with movement or coughing.<ref name="izenwasser"/><ref name="psrs"/><ref name="Latta"/>

Like other opioid drugs, pethidine has the potential to cause [[physical dependence]] or [[Substance dependence|addiction]]. The especially severe side effects unique to pethidine among opioids—serotonin syndrome, seizures, delirium, dysphoria, tremor—are primarily or entirely due to the action of its metabolite, [[norpethidine]].<ref name="psrs"/><ref name="Latta"/>