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==Pharmacology==
==Pharmacology==
Promethazine, a phenothiazine derivative, is structurally different from the [[neuroleptic]] phenothiazines, with similar but different effects.<ref name="pmid10965395">{{cite journal |vauthors=Strenkoski-Nix LC, Ermer J, DeCleene S, Cevallos W, Mayer PR | title = Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects | journal = American Journal of Health-System Pharmacy | volume = 57 | issue = 16 | pages = 1499–505 |date=August 2000 | pmid = 10965395 | doi = 10.1093/ajhp/57.16.1499| doi-access = free }}</ref> Despite e structural differences, promethazine exhibits a strikingly similar binding profile to promazine<ref>{{Cite web |title=promazine {{!}} Ligand Activity Charts {{!}} IUPHAR/BPS Guide to PHARMACOLOGY |url=https://www.guidetopharmacology.org/GRAC/LigandActivityRangeVisForward?ligandId=7281 |access-date=2023-05-18 |website=www.guidetopharmacology.org |language=en}}</ref>, another phenothiazine compound. Both promethazine and promazine exhibit comparable neuroleptic potency, with a neuroleptic potency of 0.5<ref>{{Cite book |last=H.-J. Möller, W. E. Müller, B. Bandelow |first= |title=Neuroleptika – Pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen |publisher=Wissenschaftliche Verlagsgesellschaft |year=2001 |isbn=978-3804717732 |location=Stuttgart |language=German}}</ref>. It acts primarily as a strong [[receptor antagonist|antagonist]] of the [[H1 receptor|H<sub>1</sub> receptor]] ([[antihistamine]], ''K''<sub>i</sub> = 1.4 nM<ref>{{cite journal | vauthors = Hill SJ, Young M | title = Antagonism of central histamine H1 receptors by antipsychotic drugs | journal = European Journal of Pharmacology | volume = 52 | issue = 3–4 | pages = 397–399 | date = December 1978 | pmid = 32056 | doi = 10.1016/0014-2999(78)90297-2 }}</ref>) and a moderate [[muscarinic acetylcholine|mACh receptor]] antagonist ([[anticholinergic]]),<ref name="pmid10965395"/> and also has weak to moderate [[affinity (pharmacology)|affinity]] for the [[5-HT2A receptor|5-HT<sub>2A</sub>]],<ref name="pmid8584617">{{cite journal |vauthors=Fiorella D, Rabin RA, Winter JC | title = The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis | journal = Psychopharmacology | volume = 121 | issue = 3 | pages = 347–56 |date=October 1995 | pmid = 8584617 | doi = 10.1007/bf02246074| s2cid = 24420080 }}</ref> [[5-HT2C receptor|5-HT<sub>2C</sub>]],<ref name="pmid8584617" /> [[D2 receptor|D<sub>2</sub>]],<ref name="pmid2932631">{{cite journal |vauthors=Seeman P, Watanabe M, Grigoriadis D, etal | title = Dopamine D2 receptor binding sites for agonists. A tetrahedral model | journal = Molecular Pharmacology | volume = 28 | issue = 5 | pages = 391–9 |date=November 1985 | pmid = 2932631 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2932631}}</ref><ref name="pmid847477">{{cite journal |vauthors=Burt DR, Creese I, Snyder SH | title = Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain | journal = Science | volume = 196 | issue = 4287 | pages = 326–8 |date=April 1977 | pmid = 847477 | doi = 10.1126/science.847477| bibcode = 1977Sci...196..326B }}</ref> and [[alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptor]]s,<ref name="JagadishPrasad2010">{{cite book | author = Jagadish Prasad, P. | title = Conceptual Pharmacology | url = https://books.google.com/books?id=s0e_FlM8LKYC&pg=PA295 | access-date = 27 November 2011 | year = 2010 | publisher = Universities Press | isbn = 978-81-7371-679-9 | pages = 295, 303, 598}}</ref> where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective [[NMDA receptor]] [[Receptor antagonist|antagonist]]; which might promote sedation in addition with the strong [[antihistamine]]rgic effects of the [[Histamine H1 receptor|H<sub>1</sub> receptor]], but also as a weaker [[analgesic]]. It does not however affect the [[AMPA receptor|AMPA]] receptors.<ref>{{cite journal | vauthors = Adolph O, Köster S, Georgieff M, Georgieff EM, Moulig W, Föhr KJ | title = Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug | journal = Neuropharmacology | volume = 63 | issue = 2 | pages = 280–291 | date = August 2012 | pmid = 22507664 | doi = 10.1016/j.neuropharm.2012.03.006 | s2cid = 35487146 }}</ref>
Promethazine, a phenothiazine derivative, is structurally different from the [[neuroleptic]] phenothiazines, with similar but different effects.<ref name="pmid10965395">{{cite journal |vauthors=Strenkoski-Nix LC, Ermer J, DeCleene S, Cevallos W, Mayer PR | title = Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects | journal = American Journal of Health-System Pharmacy | volume = 57 | issue = 16 | pages = 1499–505 |date=August 2000 | pmid = 10965395 | doi = 10.1093/ajhp/57.16.1499| doi-access = free }}</ref> Despite e structural differences, promethazine exhibits a strikingly similar binding profile to promazine<ref>{{Cite web |title=promazine {{!}} Ligand Activity Charts {{!}} IUPHAR/BPS Guide to PHARMACOLOGY |url=https://www.guidetopharmacology.org/GRAC/LigandActivityRangeVisForward?ligandId=7281 |access-date=2023-05-18 |website=www.guidetopharmacology.org |language=en}}</ref>, another phenothiazine compound. Both promethazine and promazine exhibit comparable neuroleptic potency, with a neuroleptic potency of 0.5<ref>{{Cite book |last=H.-J. Möller, W. E. Müller, B. Bandelow |first= |title=Neuroleptika – Pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen |publisher=Wissenschaftliche Verlagsgesellschaft |year=2001 |isbn=978-3804717732 |location=Stuttgart |language=German}}</ref>. However, dosages used therapeutically, such as for sedation or sleep disorders, have no antipsychotic effect<ref>{{Cite journal |last=Benkert |first=Otto |last2=Hippius |first2=Hanns |date=1995 |title=Psychiatrische Pharmakotherapie |url=https://link.springer.com/book/10.1007/978-3-642-79084-3 |journal=SpringerLink |language=en |doi=10.1007/978-3-642-79084-3}}</ref>. It acts primarily as a strong [[receptor antagonist|antagonist]] of the [[H1 receptor|H<sub>1</sub> receptor]] ([[antihistamine]], ''K''<sub>i</sub> = 1.4 nM<ref>{{cite journal | vauthors = Hill SJ, Young M | title = Antagonism of central histamine H1 receptors by antipsychotic drugs | journal = European Journal of Pharmacology | volume = 52 | issue = 3–4 | pages = 397–399 | date = December 1978 | pmid = 32056 | doi = 10.1016/0014-2999(78)90297-2 }}</ref>) and a moderate [[muscarinic acetylcholine|mACh receptor]] antagonist ([[anticholinergic]]),<ref name="pmid10965395"/> and also has weak to moderate [[affinity (pharmacology)|affinity]] for the [[5-HT2A receptor|5-HT<sub>2A</sub>]],<ref name="pmid8584617">{{cite journal |vauthors=Fiorella D, Rabin RA, Winter JC | title = The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis | journal = Psychopharmacology | volume = 121 | issue = 3 | pages = 347–56 |date=October 1995 | pmid = 8584617 | doi = 10.1007/bf02246074| s2cid = 24420080 }}</ref> [[5-HT2C receptor|5-HT<sub>2C</sub>]],<ref name="pmid8584617" /> [[D2 receptor|D<sub>2</sub>]],<ref name="pmid2932631">{{cite journal |vauthors=Seeman P, Watanabe M, Grigoriadis D, etal | title = Dopamine D2 receptor binding sites for agonists. A tetrahedral model | journal = Molecular Pharmacology | volume = 28 | issue = 5 | pages = 391–9 |date=November 1985 | pmid = 2932631 | url = http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2932631}}</ref><ref name="pmid847477">{{cite journal |vauthors=Burt DR, Creese I, Snyder SH | title = Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain | journal = Science | volume = 196 | issue = 4287 | pages = 326–8 |date=April 1977 | pmid = 847477 | doi = 10.1126/science.847477| bibcode = 1977Sci...196..326B }}</ref> and [[alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptor]]s,<ref name="JagadishPrasad2010">{{cite book | author = Jagadish Prasad, P. | title = Conceptual Pharmacology | url = https://books.google.com/books?id=s0e_FlM8LKYC&pg=PA295 | access-date = 27 November 2011 | year = 2010 | publisher = Universities Press | isbn = 978-81-7371-679-9 | pages = 295, 303, 598}}</ref> where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective [[NMDA receptor]] [[Receptor antagonist|antagonist]]; which might promote sedation in addition with the strong [[antihistamine]]rgic effects of the [[Histamine H1 receptor|H<sub>1</sub> receptor]], but also as a weaker [[analgesic]]. It does not however affect the [[AMPA receptor|AMPA]] receptors.<ref>{{cite journal | vauthors = Adolph O, Köster S, Georgieff M, Georgieff EM, Moulig W, Föhr KJ | title = Promethazine inhibits NMDA-induced currents - new pharmacological aspects of an old drug | journal = Neuropharmacology | volume = 63 | issue = 2 | pages = 280–291 | date = August 2012 | pmid = 22507664 | doi = 10.1016/j.neuropharm.2012.03.006 | s2cid = 35487146 }}</ref>


Another notable use of promethazine is as a [[local anesthetic]], by blockage of [[sodium channel]]s.<ref name="JagadishPrasad2010" />
Another notable use of promethazine is as a [[local anesthetic]], by blockage of [[sodium channel]]s.<ref name="JagadishPrasad2010" />

Revision as of 20:59, 18 May 2023

Promethazine
Clinical data
Trade namesPhenergan, many others[1]
AHFS/Drugs.comMonograph
MedlinePlusa682284
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, rectal, intravenous, intramuscular, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability88% absorbed but after first-pass metabolism reduced to 25% absolute bioavailability[2]
Protein binding93%
MetabolismLiver glucuronidation and sulfoxidation
Elimination half-life10–19 hours[2][3]
ExcretionKidney and biliary
Identifiers
  • (RS)-N,N-Dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.445 Edit this at Wikidata
Chemical and physical data
FormulaC17H20N2S
Molar mass284.42 g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • S2c1ccccc1N(c3c2cccc3)CC(N(C)C)C
  • InChI=1S/C17H20N2S/c1-13(18(2)3)12-19-14-8-4-6-10-16(14)20-17-11-7-5-9-15(17)19/h4-11,13H,12H2,1-3H3 checkY
  • Key:PWWVAXIEGOYWEE-UHFFFAOYSA-N checkY
  (verify)

Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold[4] and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use (especially with codeine).[5][6][7] Promethazine is taken by mouth (Oral), as a rectal suppository, or by injection into a muscle (IM).[4]

Common side effects of promethazine include confusion and sleepiness;[4] consumption of alcohol or other sedatives can make these symptoms worse.[4] It is unclear if use of promethazine during pregnancy or breastfeeding is safe for the baby.[4][6] Use of promethazine is not recommended in those less than two years old, due to potentially negative effects on breathing.[4] Use of promethazine by injection into a vein is not recommended, due to potential skin damage.[4] Promethazine is in the phenothiazine family of medications.[4] It is also a moderate anticholinergic, which produces its sedative effects. This also means high doses act as a deliriant.[2]

Promethazine was made in the 1940s by a team of scientists from Rhône-Poulenc laboratories.[8] It was approved for medical use in the United States in 1951.[4] It is a generic medication and is available under many brand names globally.[1] In 2020, it was the 208th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[9][10]

Medical uses

Promethazine has a variety of medical uses, including:

Side effects

Some documented side effects include:

  • Tardive dyskinesia, pseudoparkinsonism, acute dystonia (effects due to dopamine D2 receptor antagonism)[11]
  • Confusion in the elderly[11]
  • Drowsiness, dizziness, fatigue, more rarely vertigo
  • Known to have effects on serotonin and dopamine receptors.[14]
  • Dry mouth[11]
  • Nausea[15]
  • Respiratory depression in patients under age of two and in those with severely compromised pulmonary function[16]
  • Blurred vision, xerostomia, dry nasal passages, dilated pupils, constipation, and urinary retention. (due to its anti-cholinergic effects)[11]
  • Chest discomfort/pressure (In children less than 2 years old)[11]
  • Akathisia[17]

Less frequent:

  • Cardiovascular side effects to include arrhythmias and hypotension[11]
  • Neuroleptic malignant syndrome[11]
  • Liver damage and cholestatic jaundice[11]
  • Bone marrow suppression, potentially resulting in agranulocytosis, thrombocytopenia, and leukopenia[11]
  • Depression of the thermoregulatory mechanism resulting in hypothermia/hyperthermia[11]

Rare side effects include:

Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.[18] In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea.[19]

Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment.[20]

Overdose

Promethazine in overdose can produce signs and symptoms including CNS depression, hypotension, respiratory depression, unconsciousness, and sudden death.[21] Other reactions may include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-planar reflexes.[21] Atypically and/or rarely, stimulation, convulsions, hyperexcitability, and nightmares may occur.[21] Anticholinergic effects like dry mouth, dilated pupils, flushing, gastrointestinal symptoms, and delirium may occur as well.[21] Treatment of overdose is supportive and based on symptoms.[21]

Pharmacology

Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects.[2] Despite e structural differences, promethazine exhibits a strikingly similar binding profile to promazine[22], another phenothiazine compound. Both promethazine and promazine exhibit comparable neuroleptic potency, with a neuroleptic potency of 0.5[23]. However, dosages used therapeutically, such as for sedation or sleep disorders, have no antipsychotic effect[24]. It acts primarily as a strong antagonist of the H1 receptor (antihistamine, Ki = 1.4 nM[25]) and a moderate mACh receptor antagonist (anticholinergic),[2] and also has weak to moderate affinity for the 5-HT2A,[26] 5-HT2C,[26] D2,[27][28] and α1-adrenergic receptors,[29] where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective NMDA receptor antagonist; which might promote sedation in addition with the strong antihistaminergic effects of the H1 receptor, but also as a weaker analgesic. It does not however affect the AMPA receptors.[30]

Another notable use of promethazine is as a local anesthetic, by blockage of sodium channels.[29]

Binding to receptors in nM (Ki)[31]
receptor Ki (nM) reference
α1A-adrenoceptor (Rat) 32 DrugMatrix in vitro pharmacology data
α1B-adrenoceptor (Rat) 21 DrugMatrix in vitro pharmacology data
α1D-adrenoceptor (Human) 90 DrugMatrix in vitro pharmacology data
α2A-adrenoceptor (Human) 256 DrugMatrix in vitro pharmacology data
α2B-adrenoceptor (Human) 24 DrugMatrix in vitro pharmacology data
α2C-adrenoceptor (Human) 353 DrugMatrix in vitro pharmacology data
Calmodulin (Human) 60000[32] Eur J Med Chem (2016) 116: 36-45 [PMID:27043269]
Calmodulin (Bovine) 50000[32] Eur J Med Chem (2016) 116: 36-45 [PMID:27043269]
Chloroquine resistance transporter (Plasmodium falciparum) 85000[33] ACS Med Chem Lett (2014) 5: 576-581 [PMID:24900883]
D1 receptor (Human) 1372 DrugMatrix in vitro pharmacology data
D2 receptor (Human) 260 DrugMatrix in vitro pharmacology data
D3 receptor (Human) 190 DrugMatrix in vitro pharmacology data
H1 receptor (Human) 0.33-1.4[34] DrugMatrix in vitro pharmacology data
H2 receptor (Human) 1146 DrugMatrix in vitro pharmacology data
M1 receptor (Human) 3.32 DrugMatrix in vitro pharmacology data
M2 receptor (Human) 12 DrugMatrix in vitro pharmacology data
M3 receptor (Human) 4.15 DrugMatrix in vitro pharmacology data
M4 receptor (Human) 1.06 DrugMatrix in vitro pharmacology data
M5 receptor (Human) 3.31 DrugMatrix in vitro pharmacology data
NET (Human) 4203 DrugMatrix in vitro pharmacology data
Prion protein (Human) 8000 J Med Chem (2003) 46: 3563-3564 [PMID:12904059]
5-HT1A receptor (Rat) 1484 DrugMatrix in vitro pharmacology data
5-HT2A receptor (Human) 19 DrugMatrix in vitro pharmacology data
5-HT2B receptor (Human) 43 DrugMatrix in vitro pharmacology data
5-HT2C receptor (Human) 6.48 DrugMatrix in vitro pharmacology data
5-HT6 receptor (Human) 1128 DrugMatrix in vitro pharmacology data
SERT (Serotonin transporter) (Human) 2130 DrugMatrix in vitro pharmacology data
Sigma1 receptor (Human) 120 DrugMatrix in vitro pharmacology data
OCT1 (Human) 35100[35] J Med Chem (2008) 51: 5932-5942 [PMID:18788725]

Chemistry

Solid promethazine hydrochloride is a white to faint-yellow, practically odorless, crystalline powder. Slow oxidation may occur upon prolonged exposure to air, usually causing blue discoloration. Its hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers.[36]

History

Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the early 1940s.[37] The team was seeking to improve on diphenhydramine; the same line on medical chemistry led to the creation of chlorpromazine.[38]

Society and culture

As of July 2017, it is marketed under many brand names worldwide: Allersoothe, Antiallersin, Anvomin, Atosil, Avomine, Closin N, Codopalm, Diphergan, Farganesse, Fenazil, Fenergan, Fenezal, Frinova, Hiberna, Histabil, Histaloc, Histantil, Histazin, Histazine, Histerzin, Lenazine, Lergigan, Nufapreg, Otosil, Pamergan, Pharmaniaga, Phenadoz, Phenerex, Phenergan, Phénergan, Pipolphen, Polfergan, Proazamine, Progene, Prohist, Promet, Prometal, Prometazin, Prometazina, Promethazin, Prométhazine, Promethazinum, Promethegan, Promezin, Proneurin, Prothazin, Prothiazine, Prozin, Pyrethia, Quitazine, Reactifargan, Receptozine, Romergan, Sominex, Sylomet, Xepagan, Zinmet, and Zoralix.[1]

Atosil syrup

It is also marketed in many combination drug formulations:

Recreational use

The recreational drug lean, also known as purple drank among other names, often contains a combination of promethazine with codeine-containing cold medication.[5]

Product liability lawsuit

Main article: Wyeth v. Levine

In 2009, the US Supreme Court ruled on a product liability case involving promethazine. Diana Levine, a woman with a migraine, was administered Wyeth's Phenergan via IV push. The drug was injected improperly, resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages.

The case was appealed to the Supreme Court on grounds of federal preemption and substantive due process.[39] The Supreme Court upheld the lower courts' rulings, stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law.[40] In effect, this means drug manufacturers can be held liable for injuries if warnings of potential adverse effects, approved by the US Food and Drug Administration (FDA), are deemed insufficient by state courts.

On September 9, 2009, the FDA required a boxed warning be put on promethazine for injection, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces risk of surrounding muscle and tissue damage.[41]

References

  1. ^ a b c d "Promethazine international brands". Drugs.com. Retrieved 17 July 2017.
  2. ^ a b c d e Strenkoski-Nix LC, Ermer J, DeCleene S, Cevallos W, Mayer PR (August 2000). "Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects". American Journal of Health-System Pharmacy. 57 (16): 1499–505. doi:10.1093/ajhp/57.16.1499. PMID 10965395.
  3. ^ Paton DM, Webster DR (1985). "Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines)". Clinical Pharmacokinetics. 10 (6): 477–97. doi:10.2165/00003088-198510060-00002. PMID 2866055. S2CID 33541001.
  4. ^ a b c d e f g h i j k l m n "Promethazine Hydrochloride Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 24 October 2018.
  5. ^ a b Agnich LE, Stogner JM, Miller BL, Marcum CD (September 2013). "Purple drank prevalence and characteristics of misusers of codeine cough syrup mixtures" (PDF). Addictive Behaviors. 38 (9): 2445–9. doi:10.1016/j.addbeh.2013.03.020. PMID 23688907.
  6. ^ a b British national formulary : BNF 74 (74 ed.). British Medical Association. 2017. p. 276. ISBN 978-0857112989.
  7. ^ Malamed SF (2009). Sedation: A Guide to Patient Management. Elsevier Health Sciences. p. 113. ISBN 978-0323075961.
  8. ^ Li JJ (2006). Laughing Gas, Viagra, and Lipitor: The Human Stories behind the Drugs We Use. United Kingdom: Oxford University Press. p. 146. ISBN 9780199885282. Retrieved July 9, 2016.
  9. ^ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  10. ^ "Promethazine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  11. ^ a b c d e f g h i j k l m n Southard BT, Al Khalili Y (2019). "Promethazine". StatPearls. PMID 31335081. This article incorporates text available under the CC BY 4.0 license.
  12. ^ British National Formulary (March 2001). "4.6 Drugs used in nausea and Vertigo - Vomiting of pregnancy". BNF (45 ed.)..
  13. ^ "Rhea Seddon Oral History". NASA Johnson Space Center Oral History Project. 10 May 2011. Retrieved 25 May 2021.
  14. ^ Schreiner NM, Windham S, Barker A (December 2017). "Atypical Neuroleptic Malignant Syndrome: Diagnosis and Proposal for an Expanded Treatment Algorithm: A Case Report". A&A Case Reports. 9 (12): 339–343. doi:10.1213/XAA.0000000000000610. PMID 28767476. S2CID 39699580.
  15. ^ National Institute for Health and Care Excellence
  16. ^ Hampton T (23 February 2005). "Promethazine Warning". JAMA. 293 (8): 921. doi:10.1001/jama.293.8.921-c.
  17. ^ "Cordingley Neurology". Archived from the original on 2016-12-21. Retrieved 2008-02-15.
  18. ^ NCQA's HEDIS Measure: Use of High Risk Medications in the Elderly Archived 2010-02-01 at the Wayback Machine
  19. ^ Starke P, Weaver J, Chowdhury B (2005). "Boxed warning added to promethazine labeling for pediatric use". N. Engl. J. Med. 352 (5): 2653. doi:10.1056/nejm200506233522522. PMID 15972879.
  20. ^ Salahudeen MS, Duffull SB, Nishtala PS (March 2015). "Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review". BMC Geriatrics. 15 (31): 31. doi:10.1186/s12877-015-0029-9. PMC 4377853. PMID 25879993.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  21. ^ a b c d e https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/07935s030lbl.pdf [bare URL PDF]
  22. ^ "promazine | Ligand Activity Charts | IUPHAR/BPS Guide to PHARMACOLOGY". www.guidetopharmacology.org. Retrieved 2023-05-18.
  23. ^ H.-J. Möller, W. E. Müller, B. Bandelow (2001). Neuroleptika – Pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen (in German). Stuttgart: Wissenschaftliche Verlagsgesellschaft. ISBN 978-3804717732.{{cite book}}: CS1 maint: multiple names: authors list (link)
  24. ^ Benkert, Otto; Hippius, Hanns (1995). "Psychiatrische Pharmakotherapie". SpringerLink. doi:10.1007/978-3-642-79084-3.
  25. ^ Hill SJ, Young M (December 1978). "Antagonism of central histamine H1 receptors by antipsychotic drugs". European Journal of Pharmacology. 52 (3–4): 397–399. doi:10.1016/0014-2999(78)90297-2. PMID 32056.
  26. ^ a b Fiorella D, Rabin RA, Winter JC (October 1995). "The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis". Psychopharmacology. 121 (3): 347–56. doi:10.1007/bf02246074. PMID 8584617. S2CID 24420080.
  27. ^ Seeman P, Watanabe M, Grigoriadis D, et al. (November 1985). "Dopamine D2 receptor binding sites for agonists. A tetrahedral model". Molecular Pharmacology. 28 (5): 391–9. PMID 2932631.
  28. ^ Burt DR, Creese I, Snyder SH (April 1977). "Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain". Science. 196 (4287): 326–8. Bibcode:1977Sci...196..326B. doi:10.1126/science.847477. PMID 847477.
  29. ^ a b Jagadish Prasad, P. (2010). Conceptual Pharmacology. Universities Press. pp. 295, 303, 598. ISBN 978-81-7371-679-9. Retrieved 27 November 2011.
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External links

  • "Promethazine". U.S. National Library of Medicine and National Institutes of Health.
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