Pharmacology optical isomerism

Properties of enantiomers Enantiomers share same physical properties, e.g. melting points, boiling points and solubilities. They also have same chemical properties. However, they differ in their activities with plane polarized light, which gives rise to optical isomerism, and also in their pharmacological actions. 

C. C. Pfeiffer, Optical isomerism and pharmacological action, a generalization, Science 1956, 124, 29-31. 

Configurational centres impose a rigid shape on sections of the molecule in which they occur. However, their presence gives rise to geometric and optical isomerism. Since these stereoisomers have different shapes, biologically active stereoisomers will often exhibit differences in their potencies and/or activities (Table 2.1). These pharmacological variations are particularly likely when a chiral centre is located in a critical position in the structure of the molecule. The consequence of these differences is that it is now necessary to make and test separately all the individual stereoisomers of a drug. 

A class of barbiturates possessing the 2 -pentyl side chain all exhibit similar optical isomerism. These include pentobarbital (Fig, 7 [13a]), thiopental, thiamylal, and secobarbital (Fig. 7 [13b]), Differences in pharmacological activity between enantiomers of these compounds have been shown in humans (47) and animals (48). 

Optical isomers or enantiomers are stereoisomers which exhibit chirality. Optical isomerism is of interest because of its application in inorganic chemistry, organic chemistry, physical chemistry, pharmacology and biochemistry. 

Are there any stereochemical requirements of local anesthetic compounds when they bind to the sodium channel receptors A number of clinically used local anesthetics do contain a chiral center (i.e., bupivacaine, etidocaine, mepivacaine, and prilocaine) (Table 16.2), but in contrast to cholinergic drugs, the effect of optical isomerism on isolated nerve preparations revealed a lack of stereospecificity. In a few cases (e.g., prilocaine, bupivacaine, and etidocaine), however, small differences in the total pharmacological profile of optical isomers have been noted when administered in vivo (41,42,43). Whether these differences result from differences in uptake, distribution, and metabolism or from direct binding to the receptor has not been determined. 

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