Escitalopram

Citalopram belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). It is indicated for the treatment of depression.

Escitalopram

Chirality and biological activity

Citalopram has one stereocenter, to which a 4-fluoro phenyl group and an N, N-dimethyl-3-aminopropyl group are linked. As a consequence the molecule exists as an enantiomeric pair, the S-(+)-citalopram and R-(–)-citalopram.

The selective serotonin-reuptake inhibitor  activity resides primarily in the  S-enantiomer (eutomer) while the R-enantiomer is 30-fold less potent (distomer). To know more about eutomer and distomer nomenclature read @ <https://chiralpedia.com/blog/chiral-twins-identical-but-not-really/> In clinical trials, both racemic (R,S)-citalopram and (S)-citalopram were significantly better than placebo for improving depression and data suggests that (S)-citalopram has greater efficacy than and fewer side-effects than the (±)-citalopram. By and large, (S)-citalopram appears to have advantages over (±)-citalopram and is a good example of the potential benefits of enantiopure drugs.

Reasoning for the chiral switch

  • Faster onset of action
  • Reduction in side effects and tolerability profile
  • S-enantiomer has greater potency in comparison to the R-  enantiomer in the inhibition of 5-HT uptake, eudisimic ratios (S/R) between 130 and 160 depending on test system used. To know about eudisimic ratio, read more @ my page in Wikipedia – Chiral drugs. Wikipedia, Wikipedia Foundation, 10/09/2022.  https://en.wikipedia.org/wiki/Chiral_drugs>.
  • Better risk-benefit ratio compared to R-Citalopram

Nomenclature

(1S)-1-[3-(dimethylamino)propyl]-1-(3-fluorophenyl)-3H-2-benzofuran-5-carbonitrile

Exercise

Understand the terms eutomer, distomer and eudisimic ratio

Comprehend numbering of the heterocyclic ring system and the naming of escitalopram

Reference

https://pubchem.ncbi.nlm.nih.gov/compound/Escitalopram

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

Jonathan McConathy, and Michael J. Owens. Stereochemistry in Drug Action, Prim Care Companion J. Clin. Psychiatry.5(2): 70–73, 2003. DOI: 10.4088/pcc.v05n0202

C. Lindsay DeVane and David W. Boulton. Great Expectations in Stereochemistry: Focus on Antidepressants, CNS Spectrums , Volume 7 , Issue S1: The Biological and Clinical Significance of Single Isomers , 28 – 33, 2002. DOI: https://doi.org/10.1017/S1092852900028571

Harkishan Singh and V.K. Kapoor. Medicinal chemistry and pharmaceutical chemistry, Vallabh Prakashan, New Delhi, Page 163-164, 2012.

Chiral drugs. Wikipedia, Wikipedia Foundation, 10/09/2022.  https://en.wikipedia.org/wiki/Chiral_drugs and references therein

https://chiralpedia.com/blog/chiral-twins-identical-but-not-really/

Leave a Comment

Your email address will not be published.