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 namesPrimalan
AHFS/Drugs.comInternational Drug Names
ATC code
Legal status
Legal status
  • EU: Rx-only [1]
Identifiers
IUPAC name
  • 10-(1-Azabicyclo[2.2.2]octan-3-ylmethyl)phenothiazine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.045.005
Chemical and physical data
FormulaC20H22N2S
Molar mass322.47 g·mol−1
3D model (JSmol)
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] Patents:[7][8] New patent (91%):[9] NA:[10]

References
  1. https://www.ema.europa.eu/documents/psusa/mequitazine-list-nationally-authorised-medicinal-products-psusa/00001986/202001_en.pdf
  2. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 548. ISBN 9783527607495.
  3. Jean-Claude Bondiou, Francoise Hodac, Didier Legroux, U.S. Patent 4,546,185 (1985 to Pharmuka Laboratoires).
  4. Chem Pharm Bull (Tokyo). 2009 Nov;57(11):1300-2.
  5. Guminski, Yves; Fabre, Valerie; Lesimple, Patrick; Imbert, Thierry (1999). "AN EFFICIENT SYNTHESIS OF MEQUITAZINE". Organic Preparations and Procedures International. 31 (3): 319–323. doi:10.1080/00304949909458326.
  6. Leroux, Sébastien; Larquetoux, Laurent; Nicolas, Marc; Doris, Eric (2011). "Asymmetric Synthesis of (+)-Mequitazine from Quinine". Organic Letters. 13 (13): 3549–3551. doi:10.1021/ol2012567.
  7. Gueremy C & Labey R (+2), DE 2009555 (1970 to Sogeras); CA, 73, 131017r
  8. Gueremy; Claude; Labey; Robert; Wirth; Didier; Auclair; Maurice Patent: U.S. Patent 3,987,042 (1976).
  9. Charles Mioskowski, et al. WO 2008107545 (to Pierre Fabre Medicament SA)
  10. Shigeya Yamazaki, Hiroyuki Yumoto, & Masami Igi, U.S. Patent 6,433,168 (2002 to Sumitomo Chemical Co Ltd).

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): 221–5. 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): 250–8. 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): 437–42. 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): 451–4. doi:10.1111/j.1398-9995.1997.tb01028.x. PMID 9188930. S2CID 34785561.
  • "Mequitazine". Drug Information Portal. U.S. National Library of Medicine.
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