Quifenadine

Quifenadine (Russian: хифенадин, trade name: Phencarol, Фенкарол) is a 2nd generation antihistamine drug, marketed mainly in post-Soviet countries.[2][3] Chemically, it is a quinuclidine derivative.

Not to be confused with quinidine.
Quifenadine
Clinical data
Trade namesFencarol
Other names3-Quinuclidinyldiphenylmethanol
Routes of
administration		Oral (tablets), IM injection
ATC code
Legal status
Legal status
  • OTC (tablets), ℞-only (solution for IM injection) (RU)
Pharmacokinetic data
Bioavailability45% (Tmax = 1 hour)[1]
MetabolismLiver
Identifiers
IUPAC name
  • 1-Azabicyclo[2.2.2]octan-3-yl(diphenyl)methanol
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC20H23NO
Molar mass293.410 g·mol−1
3D model (JSmol)
SMILES
  • OC(c1ccccc1)(c2ccccc2)C4C3CCN(CC3)C4
InChI
  • InChI=1S/C20H23NO/c22-20(17-7-3-1-4-8-17,18-9-5-2-6-10-18)19-15-21-13-11-16(19)12-14-21/h1-10,16,19,22H,11-15H2
  • Key:PZMAHNDJABQWGS-UHFFFAOYSA-N

The drug has antiarrhythmic properties, probably due to the presence of a quinuclidine nucleus in the molecule's core. It acts as a calcium channel blocker and influences the activity of potassium channels. In children with cardiac arrhythmia, combination therapy with quifenadone and either amiodarone or propafenone was found to be more effective than monotherapy with either amiodarone or propafenone.[4]

Quifenadine is a derivative of quinuclidylcarbinol, which reduces the effects of histamine on organs and systems. Quifenadine is a competitive blocker of H1 receptors. In addition, it activates the diamine oxidase enzyme, which breaks down about 30% of endogenous histamine. This explains the effectiveness of quifenadine in patients insensitive to other antihistamines. The antihistaminic qualities of quifenadine are associated with the presence of a cyclic quinuclidine core in the structure and the distance between the diphenylcarbinol group and the nitrogen atom. In terms of antihistaminic activity and duration of action, quifenadine is superior to diphenhydramine. Quifenadine reduces the toxic effect of histamine, eliminates or weakens its bronchoconstrictor effect and spasmodic effect on the smooth muscles of the intestines, has a moderate antiserotonin and weak cholinolytic effect, has well-defined antipruritic and desensitizing properties. Quifenadine weakens the hypotensive effect of histamine and its effect on capillary permeability, does not directly affect cardiac activity and blood pressure, does not have a protective effect in aconitine arrhythmias.[5]

Indications

Synthesis

Same precursor as for mequitazine. Use patent:[6]

Synthesis:[7] Patent:[8] Prec:[9][10]

The Grignard reaction between methylquinuclidine-3-carboxylate [38206-86-9] (1) and phenylmagnesium bromide (2) gave the benzhydryl alcohol product ~29% yield. The ethyl ester is cas: [6238-33-1]

References
  1. "Fencarol (quifenadine) Tablets, for Oral Use. Full Prescribing Information". State Register of Medicines (in Russian). Retrieved 4 January 2016.
  2. "Quifenadine". Drugs.com. Retrieved 28 January 2014.
  3. Makarov L, Balykova L, Soldatova O, Komolyatova V, Serebruany V (2010). "The antiarrhythmic properties of quifenadine, H1-histamine receptor blocker in children with premature beats: a randomized controlled pilot trial". American Journal of Therapeutics. 17 (4): 396–401. doi:10.1097/MJT.0b013e3181a86987. PMID 19487925. S2CID 43654011.
  4. Soldatova ON, Balykova LA, Makarov LM, Komolyatova VN, Chuprova SN, Soldatov OM, Kornilova TI (2008-09-01). "Эффективность Фенкарола В Сочетании С Традиционными Противоаритмическими Средствами При Экстрасистолии У Детей" [Effectiveness of Fencarol in Combination With Traditional Anti-Arithmic Medicines in Children With Extrasystole]. RUDN Journal of Medicine (in Russian) (3): 46–51. ISSN 2313-0245. Archived from the original on 20 November 2020. Retrieved 18 November 2020.
  5. "Quifenadine". compendium.com.ua. Retrieved 24 July 2022.
  6. Mikhail Davydovich Mashkovsky, et al. U.S. Patent 4,117,139 (1978).
  7. Lainé DI, McCleland B, Thomas S, Neipp C, Underwood B, Dufour J, et al. (April 2009). "Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists". Journal of Medicinal Chemistry. 52 (8): 2493–2505. doi:10.1021/jm801601v. PMID 19317446.
  8. Micail Emmanuilovic Kaminka, DE 2502916 (1975 to VSESOJUZNYJ NAUCNO-ISSLEDOVATEL'SKIJ CHIMIKO-FARMACEVTICESKIJ INSTITUT IMENI SERGO ORDZONIKIDZE MOSKAU/MOSKVA SU).
  9. , U.S. Patent 2,901,486 (1959).
  10. Harry J. Wadsworth, et al. U.S. Patent 5,091,397 (1992 to Beecham Group PLC).
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