Mequitazine: Difference between revisions

{{Short description|Chemical compound}}

{{cleanup|reason=Convert long prose list(s) to bulleted list(s).|date=March 2021}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 407774264

| IUPAC_name = 10-(1-Azabicyclo[2.2.2]octan-3-ylmethyl)phenothiazine

| image = Mequitazine structure.svg

| width = 175

| alt =

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| pronounce =

| tradename = Primalan

| Drugs.com = {{drugs.com|international|mequitazine}}

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| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->

| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->

| DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) -->

| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

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| pregnancy_US = <!-- A / B / C / D / X / N -->

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| ATC_supplemental =

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

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| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

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| legal_NZ = <!-- Class A, B, C -->

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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

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| legal_EU = Rx-only

| legal_EU_comment = <ref>{{cite web | title = Active substance: mequitazine | url = https://www.ema.europa.eu/documents/psusa/mequitazine-list-nationally-authorised-medicinal-products-psusa/00001986/202001_en.pdf | work = List of nationally authorised medicinal products | location = Amsterdam | publisher = European Medicines Agency | date = 15 October 2020 }}</ref>

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

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<!--Identifiers-->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 29216-28-2

| PubChem = 4066

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB01071

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 3926

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = Y463242LY2

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D01324

<!--Chemical data-->

| C=20 | H=22 | N=2 | S=1

| smiles = c1ccc2c(c1)Sc1ccccc1N2CC1CN2CCC1CC2

| StdInChI = 1S/C20H22N2S/c1-3-7-19-17(5-1)22(18-6-2-4-8-20(18)23-19)14-16-13-21-11-9-15(16)10-12-21/h1-8,15-16H,9-14H2

| StdInChIKey = HOKDBMAJZXIPGC-UHFFFAOYSA-N

}}

<!-- Definition and medical uses -->

'''Mequitazine''' (trade name '''Primalan''') is an [[H1 antagonist|H₁ antagonist]] and [[anticholinergic]] of the [[phenothiazine]] [[chemical class]]. It is used to treat [[Allergy|allergies]] and [[rhinitis]].

<!-- Society and culture -->

It was patented in 1969 and came into medical use in 1976.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=548 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA548 |language=en}}</ref>

==Contraindications==

Severe liver disease; premature infants or full-term neonates.

==Special precautions==

[[Pregnancy]], [[Breastfeeding|lactation]]; severe cardiovascular disorders; [[asthma]]; angle-closure [[glaucoma]], [[urinary retention]], [[Benign prostatic hyperplasia|prostatic hyperplasia]], [[pyloroduodenal obstruction]]; renal and hepatic impairment; elderly, children; [[epilepsy]]. May impair ability to drive or operate machinery.

==Adverse reactions==

CNS depression including slight [[Somnolence|drowsiness]] to deep sleep, lassitude, [[dizziness]], [[Ataxia|incoordination]]. [[Headache]], [[Psychomotor retardation|psychomotor impairment]] and [[Muscarinic antagonist|antimuscarinic]] effects. Rarely, [[rash]]es and [[Hypersensitivity|hypersensitivity reaction]]s, blood disorders, [[convulsion]]s, [[Perspiration|sweating]], [[myalgia]], [[Paresthesia|paraesthesias]], [[Extrapyramidal symptoms|extrapyramidal effect]]s, [[tremor]], [[confusion]], sleep and GI disturbances, [[tinnitus]], [[hypotension]], [[hair loss]]. [[Photosensitivity]], [[jaundice]].

==Drug interactions==

Enhances effects of CNS depressants e.g. [[Ethanol|alcohol]], [[barbiturate]]s, [[hypnotic]]s, [[Opioid|opioid analgesic]]s, [[anxiolytic]]s and [[antipsychotic]]s. Can mask signs of [[ototoxicity]] caused by [[aminoglycoside]]s. [[QT interval|QT]] prolongation (which can lead to [[torsades de pointes]] arrhythmia) reported with [[spiramycin]].

==Synthesis==

Same precursor as for [[Quifenadine]]. Note that the synthesis has changed over the years from the original. One route seems to involve a [[Johnson–Corey–Chaykovsky reaction]] of the starting ketone, although another secondary route is also discussed.

[[File:Mequitazine synthesis.svg|thumb|500px|center|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-13-0063 Thieme] Prec:<ref>{{cite patent | inventor = Bondiou JC, Hodac F, Legroux D | country = US | number = 4546185 | gdate = Pharmuka Laboratoires }}</ref> Synthesis:<ref name="pmid19881287">{{cite journal | vauthors = Gonnot V, Nicolas M, Mioskowski C, Baati R | title = Expedient synthesis of mequitazine an antihistaminic drug by palladium catalyzed allylic alkylation of sodium phenothiazinate | journal = Chemical & Pharmaceutical Bulletin | volume = 57 | issue = 11 | pages = 1300–2 | date = November 2009 | pmid = 19881287 | doi = 10.1248/cpb.57.1300 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Guminski Y, Fabre V, Lesimple P, Imbert T | title = An efficient synthesis of mequitazine. | journal = Organic Preparations and Procedures International | date = June 1999 | volume = 31 | issue = 3 | pages = 319–323 | doi = 10.1080/00304949909458326 }}</ref><ref name="pmid21657243">{{cite journal | vauthors = Leroux S, Larquetoux L, Nicolas M, Doris E | title = Asymmetric synthesis of (+)-mequitazine from quinine | journal = Organic Letters | volume = 13 | issue = 13 | pages = 3549–51 | date = July 2011 | pmid = 21657243 | doi = 10.1021/ol2012567 }}</ref>]]

{{reflist}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Ramírez Chanona N, del Rio Navarro BE, Pérez Martín J | title = [Efficacy of mequitazine (Primalan) on the relief of symptoms of allergic rhinoconjunctivitis in children. Documented clinical experience] | language = Spanish | journal = Revista Alergia Mexico | volume = 52 | issue = 6 | pages = 221–225 | date = November–December 2005 | pmid = 16568706 }}

* {{cite journal | vauthors = Theunissen EL, Vermeeren A, van Oers AC, van Maris I, Ramaekers JG | title = A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo | journal = Clinical and Experimental Allergy | volume = 34 | issue = 2 | pages = 250–258 | date = February 2004 | pmid = 14987305 | doi = 10.1111/j.1365-2222.2004.01874.x | s2cid = 23019669 }}

* {{cite journal | vauthors = Nakamura K, Yokoi T, Kodama T, Inoue K, Nagashima K, Shimada N, Shimizu T, Kamataki T | display-authors = 6 | title = Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 284 | issue = 2 | pages = 437–442 | date = February 1998 | pmid = 9454781 | url = http://jpet.aspetjournals.org/content/jpet/284/2/437.full.pdf }}

* {{cite journal | vauthors = Persi L, Dupin O, Arnaud B, Trinquand C, Michel FB, Bousquet J | title = Efficacy of mequitazine in comparison with placebo assessed by ocular challenge with allergen in allergic conjunctivitis | journal = Allergy | volume = 52 | issue = 4 | pages = 451–454 | date = April 1997 | pmid = 9188930 | doi = 10.1111/j.1398-9995.1997.tb01028.x | s2cid = 34785561 }}

{{refend}}

== External links ==

* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/mequitazine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Mequitazine }}

{{Antihistamines}}

{{Histamine receptor modulators}}

{{Muscarinic acetylcholine receptor modulators}}

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[[Category:H1 receptor antagonists]]

[[Category:Muscarinic antagonists]]

[[Category:Phenothiazines]]