STEREOCHEMISTRY - RACEMIC MODIFICATION, RESOLUTION, AND ITS IMPORTANCE WITH RECENTLY USED OPTICALLY ACTIVE DRUGS.
Â Stereochemistry involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. An important branch of stereochemistry is the study of chiral molecules. Optical activity is the ability of a chiral molecule to rotate the plane of plane-polarized light, measured using a polarimeter. Racemic modification and resolution, both processes are very important in stereochemistry. A mixture of equal parts of enantiomers is called a racemic modification. The process of separating a racemate into pure enantiomers is known as resolution. Recently, various optically active drugs are used for the treatment for various diseases. In these drugs, some are used as mixture of enantiomers and some used as single enantiomer. For preparation of optically active drugs, racemic modification and resolution processes are generally used. Hence, this is very important to know about various steps and types of processes used for the same. Racemic modification is advantageous where racemates have more therapeutic advantages than single isomers. Resolution is advantageous where single entiomer is used for treatment because single enantiomers have less complex and more selective pharmacodynamic profile as compared to racemic mixture so have lesser adverse drug reactions, improved therapeutic profile, less chances of drug interactions than racemic mixtures. Recently used optically active drugs are amlodipine, atenolol, cetirizine, ketamine, metoprolol, omeprazole, pantoprazole, salbutamol, propranolol, clopidogrel, rabeprazole, citalopram, ibuprofen, ketoprofen, zopiclone, etodolac, salbutamol, and nateglinide.
2. Singh K, Shakya P, Kumar AS, Kamal MA, Singh SP. Stereochemistry and its role in drug design. Int J Pharm Sci Res 2014;5:4644-59.
3. Murray R, Bender D, Botham KM, Kennelly PJ, Rodwell V, Weil PA, et al, editors. Harperâ€™s Illustrated Biochemistry. 29th ed. New York: Lange Medical Books, McGraw Hill Medical Publishing Division; 2012.
4. Riley TN, De Ruiter J, Ravis WR, Clark RC. Isomerism. In: Swarbrick J, editor. Encyclopedia of Pharmaceutical Technology. 3rd ed. London: Informa Healthcare; 2006. p. 6.
5. Katzung BG, Masters SB, Trever AJ, editors. Basic and Clinical Pharmacology. 11th ed. Noida, UP, India: Tata McGraw Hill; 2009.
6. Janice MH. The Physical Chemistry of Chirality. New York, NY: An American Chemical Society Publication; 2001.
7. Collins AN, Sheldrake GN, Crosby J. Chirality in Industry. New York: Wiley; 1992.
8. Collins AN, Sheldrake GN, Crosby J. Chirality in Industry II. New York: Wiley; 1997.
9. McConathy J, Owens MJ. Stereochemistry in drug action. Prim Care Companion J Clin Psychiatry 2003;5:70-3.
10. De Ruiter J. Isomerism and Stereochemistry. Princ Drug Action I Winter 2005;1:1-11.
11. Davies NM, Wei X. Importance of chirality in drug therapy and pharmacy practice: Implication of psychiatry. Adv Pharm 2003;1:242-52.
12. Eliel E, Wilen SH, Mander LN. Stereochemistry of Organic Compounds. New York: Wiley; 1994. p. 305-7.
13. Moss GP. Basic terminology of stereochemistry. Pure Appl Chem 1996;68:2205.
14. Wainer IW. Drug Stereochemistry: Analytical Methods and Pharmacology. 2nd ed. New York: Marcel Dekker; 1993.
15. Morrison RT, Boyd RN. Stereochemistry. Organic Chemistry. 6th ed. Cambridge, New York: University Press; 1992. p. 1170-1.
16. Cahn RS, Ingold CK, Prelog V. Specification of Molecular Chirality. Angew Chem Int Ed Eng 1966;5:385.
17. Swaran SV. Prochirality and pseudosymmetry-Some definitions. Proc Indian Natl Sci Acad 1983;49:202-12.
18. Anslyn EV, Dennis AD. Modern Physical Organic Chemistry. Chicago IL: University Science; 2005. p. 1083
19. Anslyn EV, Dennis AD. Modern Physical Organic Chemistry. Chicago IL: University Science; 2005. p. 1083.
20. Arthur IV. Vogelâ€™s Textbook of Practical Organic Chemistry. 5th ed. Harlow: Longman; 1996.
21. McMurry J, Simanek E. Fundamentals of Organic Chemistry. 6th ed. : Brooks Cole; 2006.
22. Schore A, Vollhardt C. Organic Chemistry Structure and Function. New York: W.H. Freeman and Company; 2007.
23. Mason JP, Hutt AJ. Stereochemical aspect of drug metabolism. In: Aboul-Enein HY, Wainer IW, editors. The Impact of Stereochemistry on Drug Development and Use. New York: Wiley; 1997. p. 45-123.
24. Eliel E, Wilen SH, Mander LN. Stereochemistry of Organic Compounds. New York: Wiley; 1994. p. 305-7.
25. Williams FT. Resolution by the method of racemic modification: A demonstration of analogy. J Chem Educ 1962;39:211.
26. Porter WH. Resolution of chiral drugs. Pure Appl Chem 1991;63:1119-22.
27. Leese P, Maier G, Eszopiclone VL. Pharmacokinetic and pharmacodynamic effects of a novel sedative hypnotic after daytime administration in healthy subjects. Sleep 2002;25:45.
28. Basu D. Comparative study to evaluate the effect of S-Amlodipine versus Amlodipine on office and ambulatory blood pressure in mild to moderate hypertensives. Indian Med Gaz 2007;12:493-7.
29. Belpaire FM, Rosseel MT, Vermeulen AM, De Smet F, Bogaert MG. Stereoselective pharmacokinetics of atenolol in the rat: Influence of aging and of renal failure. Mech Ageing Dev 1993;67:201-10.
30. Ivani G, Borgi B, Van Oven H. Levobupivacaine. Minerva Anestesiol 2001;67:20-3.
31. Devalia JL, De Vos C, Hanotte F, Baltes E. A randomized, double-blind, crossover comparison among cetirizine, and ucb28557 on histamine-induced cutaneous responses in healthy adult volunteers. Allergy 2008;56:50-7.
32. Wang DY, Hanotte F, De Vos C, Clement P. Effect of cetirizine, levocetirizine and dextrocetirizine on histamine induce nasal response in healthy adult volunteers. Allergy 2001;56:339-43.
33. Tillement JP, Testa B, BrÃ©e F. Compared pharmacological characteristics in humans of racemic cetirizine and levocetirizine, two histamine H1-receptor antagonists. Biochem Pharmacol 2003;66:1123-6.
34. Gillard M, Van Der Perren C, Moguilevsky N, Massingham R, Chatelain P. Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: Contribution of lys(191) and thr(194). Mol Pharmacol 2002;61:391-9.
35. Ihmsen H, Geisslinger G, SchÃ¼ttler J. Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine. Clin Pharmacol Ther 2001;70:431-8.
36. Zeilhofer HU, Swandulla D, Geisslinger G, Brune K. Differential effects of ketamine enantiomers on NMDA receptor currents in cultured neurons. Eur J Pharmacol 1992;213:155-8.
37. Dasbiswas A, Shinde S, Dasbiswas D. S-metoprolol: The 2008 clinical review. J Indian Med Assoc 2008;106:259-62.
38. Boucher M, DuchÃªne-Marullaz P, Moundanga JL. Studies on the stereoisomers of beta-adrenoceptor antagonists in conscious A-V blocked dogs. Br J Pharmacol 1986;89:119-27.
39. Tanaka M, Ohkubo T, Otani K, Suzuki A, Kaneko S, Sugawara K, et al. Stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor, in extensive and poor metabolizers of S-mephenytoin. Clin Pharmacol Ther 2001;69:108-13.
40. Baker DE. Esomeprazole magnesium (Nexium). Rev Gastroenterol Disord 2001;1:32-41.
41. Cao H, Wang M, Jia J, Wang Q, Cheng M. Comparison of the effects of Pantoprazole enantiomers on gastric mucosal lesions and gastric epithelial cells in rats. J Health Sci 2004;50:1-8.
42. Kim M, Shen DD, Eddy AC, Nelson WL, Roskos LK. Inhibition of the enantioselective oxidative metabolism of metoprolol by verapamil in human liver microsomes. Drug Metab Dispos 1993;21:309-17.
43. Tybring G, BÃ¶ttiger Y, WidÃ©n J, Bertilsson L. Enantioselective hydroxylation of omeprazole catalyzed by CYP2C19 in swedish white subjects. Clin Pharmacol Ther 1997;62:129-37.
44. Miura M, Satoh S, Tada H, Habuchi T, Suzuki T. Stereoselective metabolism of rabeprazole-thioether to rabeprazole by human liver microsomes. Eur J Clin Pharmacol 2006;62:113-7.
45. Evans AM. Comparative pharmacology of S(+)-ibuprofen and (RS)-ibuprofen. Clin Rheumatol 2001;20 Suppl 1:S9-14.
46. Savi P, Combalbert J, Gaich C, Rouchon MC, Maffrand JP, Berger Y, et al. The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-1A. Thromb Haemost 1994;72:313-7.
47. Savi P, Herbert JM, Pflieger AM, Dol F, Delebassee D, Combalbert J, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol 1992;44:527-32.
48. Savi P, Labouret C, Delesque N, Guette F, Lupker J, Herbert JM, et al. P2y(12), a new platelet ADP receptor, target of clopidogrel. Biochem Biophys Res Commun 2001;283:379-83.
49. Savi P, Laplace MC, Maffrand JP, Herbert JM. Binding of [3H]-2-methylthio ADP to rat platelets â€“ Effect of clopidogrel and ticlopidine. J Pharmacol Exp Ther 1994;269:772-7.
50. Savi P, Pereillo JM, Uzabiaga MF, Combalbert J, Picard C, Maffrand JP, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000;84:891-6.
51. Sugidachi A, Asai F, Ogawa T, Inoue T, Koike H. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 2000;129:1439-46.
52. Kim M, Yu SK, Truong QK, Mai XL, Chung HK, Kang JS, et al. Determination of rabeprazole enantiomers in commercial tablets using immobilized cellulose-based stationary phase. Arch Pharm Res 2017;40:373-81.
53. Burke WJ, Kratochvil CJ. Stereoisomers in psychiatry: The case of escitalopram. Prim Care Companion J Clin Psychiatry 2002;4:20-4.
54. Jacquot C, David DJ, Gardier AM, SÃ¡nchez C. Escitalopram and citalopram: The unexpected role of the R-enantiomer. Encephale 2007;33:179-87.
55. Indra KR. Chirality in Drug Design and Development. New York: Marcel Dekkar; 2004.
56. Ghezzi P, Melillo G, Meazza C, Sacco S, Pellegrini L, Asti C. Differential contribution of R and S isomers in ketoprofen anti-inflammatory activity: Role of cytokine modulation. J Pharmacol Exp Ther1 998;287:969-74.
57. Pinto Jr. LR, Bittencourt LR, Treptow EC, Braga LR, Tufik S. Eszopiclone versus zopiclone in the treatment of insomnia. Clinics (Sao Paulo) 2016;71:5-9.
58. Demerson CA, Humber LG, Abraham NA, Schilling G, Martel RR, Pace-Asciak C, et al. Resolution of etodolac and antiinflammatory and prostaglandin synthetase inhibiting properties of the enantiomers. J Med Chem 1983;26:1778-80.
59. Brocks DR, Jamali F. Etodolac clinical pharmacokinetics. Clin Pharmacokinet 1994;26:259-74.
60. Matsushima-Nishiwaki R, Shidoji Y, Nishiwaki S, Yamada T, Moriwaki H, Muto Y, et al. Aberrant metabolism of retinoid X receptor proteins in human hepatocellular carcinoma. Mol Cell Endocrinol 1996;121:179-90.
61. Matera MG, Calzetta L, Rogliani P, Bardaro F, Page CP, Cazzola M, et al. Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi. Pulm Pharmacol Ther 2011;24:221-6.
62. Miura M, Satoh S, Tada H, Habuchi T, Suzuki T. Stereoselective metabolism of rabeprazole-thioether to rabeprazole by human liver microsomes. Eur J Clin Pharmacol 2006;62:113-7.
63. Jacquot C, David DJ, Gardier AM, SÃ¡nchez C. Escitalopram and citalopram: The unexpected role of the R-enantiomer. Encephale 2007;33:179-87.
64. Baregama C, Kumari A. A Review on Herbal Antidiabetic Drugs Conference Publication in Book of National Symposium on Drug Development Through Natural Products. Vol. 1. Ch. 6. Baddi, HP: Maharaja Agrasen University; 2017. p. 11.
65. Tamura M, Shiba S, Kudo N, Kawashima Y. Pharmacokinetics of nateglinide enantiomers and their metabolites in goto-kakizaki rats, a model for Type 2 diabetes mellitus. Chirality 2010;22:92-8.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.