Stereoisomer drugs

H N Bhargava, in Handbook of Stereoisomers Drugs in Psythopharmatology (D F Smith, ed ), CRC Press, Boca Raton, Florida (1984)... 

Dewey WL, Martin BR, May EL (1984) Cannabinoid stereoisomers pharmacological effects. In Smith DF (ed) CRC Handbook. Stereoisomers drugs psychopharmacology. CRC Press, Boca Raton, pp 317-326... 

D. F. Smith, CRC Handbook of Stereoisomers Therapeutic Drugs, CRC Press, Inc., Boca Raton, Fla., 1989. 

It was apparent that the FDA recognized the ability of the pharmaceutical industry to develop chiral assays. With the advent of chiral stationary phases (CSPs) in the early 1980s [8, 9], the tools required to resolve enantiomers were entrenched, thus enabling the researcher the ability to quantify, characterize, and identify stereoisomers. Given these tools, the researcher can assess the pharmacology or toxicology and pharmacokinetic properties of enantiopure drugs for potential interconversion, absorption, distribution, and excretion of the individual enantiomers. 

Alkylamines have a variety of applications in the chemical industry as starting materials for the preparation of insecticides and pharmaceuticals. Labetalol, for instance, a so-called /3-blocker used for the treatment of hi h blood pressure, is prepared by SN2 reaction of an epoxide with a primary amine. The substance marketed for drug use is a mixture of all four possible stereoisomers, but the biological activity derives primarily from the (R,R) isomer. 

Nikolai LN, McClure EL, MacLeod SL, Wong CS (2006) Stereoisomer quantification of the Beta-blocker drugs atenolol, metoprolol, and propranolol in wastewaters by chiral high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1131 103-109... 

The chiral copper cataly.st (see Fig. 3.54) has been used to synthesize the drug Cilastatin. The desired biological activity is found in the stereoisomer derived from (-I-) 15-2,2-... 

An interesting example of the above difference is l-DOPA 4, which is used in the treatment of Parkinson s disease. The active drug is the achiral compound dopamine formed from 4 via in vivo decarboxylation. As dopamine cannot cross the blood-brain barrier to reach the required site of action, the prodrug 4 is administered. Enzyme-catalyzed in vivo decarboxylation releases the drug in its active form (dopamine). The enzyme l-DOPA decarboxylase, however, discriminates the stereoisomers of DOPA specifically and only decarboxylates the L-enantiomer of 4. It is therefore essential to administer DOPA in its pure L-form. Otherwise, the accumulation of d-DOPA, which cannot be metabolized by enzymes in the human body, may be dangerous. Currently l-DOPA is prepared on an industrial scale via asymmetric catalytic hydrogenation. 

Strong, M. FDA policy and regulation of stereoisomers Paradigm shift and the future of safer, more effective drugs. Food Drug Law J. 1999, 54,463 487, and references therein. 

The FDA (and similar regulatory agencies, as reviewed by Daniels et al., 1997) has become increasingly concerned with the safety of stereoisomeric or chiral drugs. Stereoisomers are molecules that are identical to one another in terms of atomic... 

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