Mequitazine

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

Mequitazine

Clinical data
Trade names	Primalan
AHFS/Drugs.com	International Drug Names
ATC code	R06AD07 (WHO)
Legal status
Legal status	EU: Rx-only[1]
Identifiers
IUPAC name 10-(1-Azabicyclo[2.2.2]octan-3-ylmethyl)phenothiazine
CAS Number	29216-28-2 Y
PubChem CID	4066
DrugBank	DB01071 N
ChemSpider	3926 N
UNII	Y463242LY2
KEGG	D01324 Y
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
NY (what is this?)  (verify)

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

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

Further reading

• Ramírez Chanona N, del Rio Navarro BE, Pérez Martín J (November–December 2005). "[Efficacy of mequitazine (Primalan) on the relief of symptoms of allergic rhinoconjunctivitis in children. Documented clinical experience]". Revista Alergia Mexico (in Spanish). 52 (6): 221–225. PMID 16568706.
• Theunissen EL, Vermeeren A, van Oers AC, van Maris I, Ramaekers JG (February 2004). "A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo". Clinical and Experimental Allergy. 34 (2): 250–258. doi:10.1111/j.1365-2222.2004.01874.x. PMID 14987305. S2CID 23019669.
• Nakamura K, Yokoi T, Kodama T, Inoue K, Nagashima K, Shimada N, et al. (February 1998). "Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 284 (2): 437–442. PMID 9454781.
• Persi L, Dupin O, Arnaud B, Trinquand C, Michel FB, Bousquet J (April 1997). "Efficacy of mequitazine in comparison with placebo assessed by ocular challenge with allergen in allergic conjunctivitis". Allergy. 52 (4): 451–454. doi:10.1111/j.1398-9995.1997.tb01028.x. PMID 9188930. S2CID 34785561.

External links

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