An enantiopure drug is a pharmaceutical that is available in one specific enantiomeric form. Most biological molecules (proteins, sugars, etc.) are present in only one of many chiral forms, so different enantiomers of a chiral drug molecule bind differently (or not at all) to target receptors. One enantiomer of a drug may have a desired beneficial effect while the other may cause serious and undesired side effects, or sometimes even beneficial but entirely different effects.[1] Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed as a racemic mixture and market the individual enantiomers, either by specifically manufacturing the desired enantiomer or by resolving a racemic mixture. The U.S. Food and Drug Administration (FDA) has allowed single enantiomers of generic drugs to be patented and marketed under another name.[2]
The following table lists pharmaceuticals that have been available in both racemic and single-enantiomer form.
The following are cases where the individual enantiomers have markedly different effects:
- Thalidomide: Thalidomide is racemic. One enantiomer is effective against morning sickness, whereas the other is teratogenic. However, the enantiomers are converted into each other in vivo,[3]. Dosing with a single-enantiomer form of the drug will still lead to both the D and L isomers eventually being present in the patient's serum and thus would not prevent side effects (though it might reduce them if the rate of in vivo conversion can be slowed).
- Ethambutol: Whereas one enantiomer is used to treat tuberculosis, the other causes blindness.
- Naproxen: One enantiomer is used to treat arthritis pain, but the other causes liver poisoning with no analgesic effect.
- Steroid receptor sites also show stereoisomer specificity.
- Penicillin's activity is stereodependent. The antibiotic must mimic the D-alanine chains that occur in the cell walls of bacteria in order to react with and subsequently inhibit bacterial transpeptidase enzyme.
- Only L-propranolol is a powerful adrenoceptor antagonist, whereas D-propranolol is not. However, both have local anesthetic effect.
- The L-isomer of Methorphan, levomethorphan is a potent opioid analgesic, while the D-isomer, dextromethorphan is a dissociative cough suppressant.
- (S)-(–) isomer of carvedilol, a drug that interacts with adrenoceptors, is 100 times more potent as beta receptor blocker than (R)-(+) isomer. However, both the isomers are approximately equipotent as alpha receptor blockers.
- The D-isomers of amphetamine and methamphetamine are strong CNS stimulants, while the L-isomers of both drugs lack appreciable CNS(central nervous system) stimulant effects, but instead stimulate the peripheral nervous system. For this reason, the Levo-isomer of methamphetamine is available as an OTC nasal inhaler in some countries, while the Dextro-isomer is banned from medical use in all but a few countries in the world, and highly regulated in those countries who do allow it to be used medically.
[edit] References
- ^ E. J. Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology, European Journal of Clinical Pharmacology 26 (1984) 663-668.
- ^ US FDA's policy statement on the development of new stereoisomeric drugs[dead link]
- ^ Teo SK, Colburn WA, Tracewell WG, Kook KA, Stirling DI, Jaworsky MS, Scheffler MA, Thomas SD, Laskin OL (2004). "Clinical pharmacokinetics of thalidomide". Clin Pharmacokinet. 43 (5): 311–327. PMID 15080764.
