J Appl Biomed 2:95-100, 2004 | DOI: 10.32725/jab.2004.011

Biomedical aspects of chiral molecules

Jiří Patočka1,*, Aleš Dvořák2
1 Department of Toxicology, Military Medical Academy, Hradec Králové and Faculty of Health and Social Studies, University of South Bohemia, České Budějovice, Czech Republic
2 Lundbeck CRS, s.r.o., Praha, Czech Republic

This article defines some of the terms used in chiral chemistry and some of the basic mechanistic issues that arise in stereochemistry in pharmacology. Attention is also drawn to the impact of stereochemistry on drug regulation and its significance for new drug development. The stereoselectivity of drugs is underpinned by the fact that the human body is essentially a chiral structure. The rationale for development of chiral drugs is the suggestion that single stereoisomer drugs would provide superior therapy by allowing reductions in dosage, reduced variability in metabolism and response, simpler dose-response relationships and improved tolerability.

Keywords: chiral drug; stereoisomer; enantiomer; stereochemistry; stereopharmacology

Received: January 12, 2004; Revised: February 24, 2004; Published: July 31, 2004  Show citation

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Patočka J, Dvořák A. Biomedical aspects of chiral molecules. J Appl Biomed. 2004;2(2):95-100. doi: 10.32725/jab.2004.011.
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References

  1. Almansa C., L.A. Gomez, F.L. Cavalcanti, A.F. de Arriba, R. Rodriguez, E. Carceller, J. Garcia-Rafanell, J. Forn: Diphenylpropionic acids as new AT1 selective angiotensin II antagonists. J. Med. Chem. 39: 2197-2206, 1996. Go to original source... Go to PubMed...
  2. Ariens E.J.: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur. J. Clin. Pharmacol. 26: 663-668, 1984. Go to original source... Go to PubMed...
  3. Burke W.J., Ch.J. Kratochvil: Stereoisomers in psychiatry: the case of escitalopram. J. Clin. Psychiatry 4: 20-24, 2002. Go to original source...
  4. Cahn R.S., C.K. Ingold, V. Prelog: Specification of molecular chirality. Angew. Chem. 78: 413-447, 1966. Go to original source...
  5. Cheng H., J.D. Rogers, J.L. Demetriades, S.D. Holland, J.R. Seibold, E. Depuy: Pharmacokinetics and bioinversion of ibuprofen enantiomers in humans. Pharm. Res. 11: 824-830, 1994. Go to original source... Go to PubMed...
  6. Chon E.M., R.K.Middleton: Labetalol hepato toxicity. Ann. Pharmacother. 26: 344-345, 1992. Go to original source... Go to PubMed...
  7. Herdevall B.M., B. Klinge, L. Persson, G. Huledal, M. Abdel-Rehim: Plasma levels of lidocaine, o-toluidine, and prilocaine after application of 8.5 g Oraqix in patients with generalized periodontitis: effect on blood methemoglobin and tolerability. Acta Odontol. Scand. 61: 230-234, 2003. Go to original source... Go to PubMed...
  8. Hutt A.J. and S.C. Tan: Drug chirality and its clinical significance. Drugs 52, Suppl. 2: 1-12, 1996. Go to original source... Go to PubMed...
  9. Lalonde R.L., T.L. O'Rear, I.W. Wainer, K.D. Drda, V.L. Herring, M.B. Bottorff: Labetalol pharmacokinetics and pharmacodynamics: evidence of stereoselective disposition. Clin. Pharmacol. Ther. 48: 509-519, 1990. Go to original source... Go to PubMed...
  10. Palareti G. and C.Legnani: Warfarin withdrawal. pharmacokinetic-pharmacodynamic considerations. Clin. Pharmacokinet. 30: 300-313, 1996. Go to original source... Go to PubMed...
  11. Patočka J., B. Plucar: Pharmacology and toxicology of absinthe. J. Appl. Biomed. 1, 199-205, 2003. Go to original source...
  12. Pohl L.R., R. Bales, W.F. Trager: Warfarin - stereochemical aspects of its metabolism in vivo in the rat. Res. Commun. Chem. Pathol. Pharmacol. 15: 233-256, 1976. Go to PubMed...
  13. Rybak L.P., C. Whitworth: Ototoxicity of indacrinone is stereospecific. Hear Res. 31: 169-174, 1987. Go to original source... Go to PubMed...
  14. Sanchez C., P.B. Bergqvist, L.T. Brennum, S. Gupta, S. Hogg, A. Larsen, O. Wiborg: Escitalopram, the S-(+)-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities. Psychopharmacology (Berl). 167: 353-362, 2003. Go to original source... Go to PubMed...
  15. Schwarz U.I.: Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. Eur. J. Clin. Invest. 33, Suppl 2: 23-30, 2003. Go to original source... Go to PubMed...