Mequitazine

Mequitazine
Clinical data
Trade names	Primalan
AHFS/Drugs.com	International Drug Names
ATC code	R06AD07 (WHO) ;
Legal status
Legal status	EU: Rx-only;
Identifiers
	IUPAC name 10-(1-Azabicyclo[2.2.2]octan-3-ylmethyl)phenothiazine;
CAS Number	29216-28-2 ;
PubChem CID	4066;
DrugBank	DB01071 ;
ChemSpider	3926 ;
UNII	Y463242LY2;
KEGG	D01324 ;
CompTox Dashboard (EPA)	DTXSID8023262 ;
ECHA InfoCard	100.045.005
Chemical and physical data
Formula	C20H22N2S
Molar mass	322.47 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c1ccc2c(c1)Sc1ccccc1N2CC1CN2CCC1CC2;
	InChI InChI=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; Key:HOKDBMAJZXIPGC-UHFFFAOYSA-N;
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Mequitazine (trade name Primalan) is an H₁ antagonist and anticholinergic of the phenothiazine chemical class. It is used to treat allergies and rhinitis.

It was patented in 1969 and came into medical use in 1976.^[2]

Contraindications

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

Special precautions

Pregnancy, lactation; severe cardiovascular disorders; asthma; angle-closure glaucoma, urinary retention, 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 drowsiness to deep sleep, lassitude, dizziness, incoordination. Headache, psychomotor impairment and antimuscarinic effects. Rarely, rashes and hypersensitivity reactions, blood disorders, convulsions, sweating, myalgia, paraesthesias, extrapyramidal effects, tremor, confusion, sleep and GI disturbances, tinnitus, hypotension, hair loss. Photosensitivity, jaundice.

Drug interactions

Enhances effects of CNS depressants e.g. alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytics and antipsychotics. Can mask signs of ototoxicity caused by aminoglycosides. 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.

Thieme Prec:^[3] Synthesis:^[4]^[5]^[6]

References

^ "Active substance: mequitazine" (PDF). List of nationally authorised medicinal products. Amsterdam: European Medicines Agency. 15 October 2020.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN 9783527607495.
^ US 4546185, Bondiou JC, Hodac F, Legroux D, issued Pharmuka Laboratoires
^ Gonnot V, Nicolas M, Mioskowski C, Baati R (November 2009). "Expedient synthesis of mequitazine an antihistaminic drug by palladium catalyzed allylic alkylation of sodium phenothiazinate". Chemical & Pharmaceutical Bulletin. 57 (11): 1300–2. doi:10.1248/cpb.57.1300. PMID 19881287.
^ Guminski Y, Fabre V, Lesimple P, Imbert T (June 1999). "An efficient synthesis of mequitazine". Organic Preparations and Procedures International. 31 (3): 319–323. doi:10.1080/00304949909458326.
^ Leroux S, Larquetoux L, Nicolas M, Doris E (July 2011). "Asymmetric synthesis of (+)-mequitazine from quinine". Organic Letters. 13 (13): 3549–51. doi:10.1021/ol2012567. PMID 21657243.

External links

"Mequitazine". Drug Information Portal. U.S. National Library of Medicine.

[1] "Active substance: mequitazine" (PDF). List of nationally authorised medicinal products. Amsterdam: European Medicines Agency. 15 October 2020.

[Fis2006-2] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN 9783527607495.

[3] US 4546185, Bondiou JC, Hodac F, Legroux D, issued Pharmuka Laboratoires

[pmid19881287-4] Gonnot V, Nicolas M, Mioskowski C, Baati R (November 2009). "Expedient synthesis of mequitazine an antihistaminic drug by palladium catalyzed allylic alkylation of sodium phenothiazinate". Chemical & Pharmaceutical Bulletin. 57 (11): 1300–2. doi:10.1248/cpb.57.1300. PMID 19881287.

[5] Guminski Y, Fabre V, Lesimple P, Imbert T (June 1999). "An efficient synthesis of mequitazine". Organic Preparations and Procedures International. 31 (3): 319–323. doi:10.1080/00304949909458326.

[pmid21657243-6] Leroux S, Larquetoux L, Nicolas M, Doris E (July 2011). "Asymmetric synthesis of (+)-mequitazine from quinine". Organic Letters. 13 (13): 3549–51. doi:10.1021/ol2012567. PMID 21657243.

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