Levocetirizine

Levocetirizine is chiral switch drug for allergies. It is a third generation, non-sedating, selective histamine H1 receptor antagonist, with antihistamine, anti-inflammatory and potential anti-angiogenic activities. Levocetirizine is used to relieve the symptoms of hay fever and hives of the skin. It is an antihistamine that works by preventing the effects of a substance called histamine, which is produced by the body. 

Chirality and Biological activity

Cetirizine carries one stereogenic carbon (indicted by an red arrow mark) and hence exists as a racemic mixture of levocetirizine [(R)-enantiomer] and dextrocetirizine [(S)-enantiomer]. (S)-enantiomer is essentially inactive.

Claim for the chiral switch

  •   R-enantiomer is 2-4 x more potent than the racemate
  •   Decreased side effects

Note: There are contradictory observations on this chiral switch. Some studies based on available clinical evidence coupled with the cost differential, criticize that there is no rationale for prescribing levocetirizine in place of cetirizine. Further, state that the therapeutic advantages of single enantiomer drugs levocetirizine over their racemate have been disappointing. [Source:[https://pubmed.ncbi.nlm.nih.gov/24066264/].

Nomenclature

2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid (R)-2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid

2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid

Exercise

Understand the naming of levocetirizine and the stereochemical descriptors employed

Reference

Harkishan Singh and V.K. Kapoor. Medicinal chemistry and pharmaceutical chemistry, Vallabh Prakashan, New Delhi, Page 277, 2012.

Kathryn Blake  and Hengameh Raissy. Chiral Switch Drugs for Asthma and Allergies: True Benefit or Marketing Hype,  Pediatr Allergy Immunol Pulmonol., 26(3), 157–160, 2013.

Chiral switch. Wikipedia, Wikipedia Foundation, 12/08/2022.  https://en.wikipedia.org/wiki/Chiral_switch and references therein

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