Enantiomers: their importance in psychopharmacology
The majority of naturally occurring drugs and biologically active compounds are asymmetrical in their chemical structure. This means that the molecule is structured around one or more carbon atoms in such a way that the molecule is distributed mostly on the right (R=rectus) or left (S=sinister) of the symmetrical carbon atom, the so-called chiral centre of the molecule. Thus a large proportion of psychotropic drugs in current use possess one or more chiral centres and therefore exist in pairs of enantiomers which differ in terms of their three-dimensional structures. However, it must be remembered that chirality can apply not only to molecules but also to anatomical structures. For example, the left and right hands are chiral structures as is evident when one attempts to put a lefthanded glove on the right hand and vice versa. At the cellular level, the various types of receptor, transporter, enzyme and ion channel are all chiral in form. Thus although the enantiomers of a drug may have identical physicochemi cal properties, the way in which they may interact with chiral targets at the level of the cell will give rise to different pharmacodynamic and pharmacokinetic properties. A few simple examples will illustrate how taste and olfactory receptors can differentiate between enantiomers. Thus R-carvone tastes like spearmint whereas the S-isomer tastes like caraway. Similarly, R-limolene smells like lemon whereas the S-enantiomer tastes of orange. In psychopharmacology, interest in the properties of enantiomers has been aided by the need to improve the therapeutic efficacy and decrease the side effects and toxicity of drugs. For example, if the therapeutic activity resides entirely in one enantiomer (called a eutomer) then giving a racemic mixture which contains the active and the inactive enantiomer is clearly wasteful. Thus using the single enantiomer (isomer or eutomer) should enable the dose of the drug to be lowered, reduce the interpatient variability in the response and, hopefully, reduce the side effects and toxicity of the drug.
The majority of naturally occurring drugs and biologically active compounds are asymmetrical in their chemical structure. This means that the molecule is structured around one or more carbon atoms in such a way that the molecule is distributed mostly on the right (R=rectus) or left (S=sinister) of the symmetrical carbon atom, the so-called chiral centre of the molecule. Thus a large proportion of psychotropic drugs in current use possess one or more chiral centres and therefore exist in pairs of enantiomers which differ in terms of their three-dimensional structures. However, it must be remembered that chirality can apply not only to molecules but also to anatomical structures. For example, the left and right hands are chiral structures as is evident when one attempts to put a lefthanded glove on the right hand and vice versa. At the cellular level, the various types of receptor, transporter, enzyme and ion channel are all chiral in form. Thus although the enantiomers of a drug may have identical physicochemi cal properties, the way in which they may interact with chiral targets at the level of the cell will give rise to different pharmacodynamic and pharmacokinetic properties. A few simple examples will illustrate how taste and olfactory receptors can differentiate between enantiomers. Thus R-carvone tastes like spearmint whereas the S-isomer tastes like caraway. Similarly, R-limolene smells like lemon whereas the S-enantiomer tastes of orange. In psychopharmacology, interest in the properties of enantiomers has been aided by the need to improve the therapeutic efficacy and decrease the side effects and toxicity of drugs. For example, if the therapeutic activity resides entirely in one enantiomer (called a eutomer) then giving a racemic mixture which contains the active and the inactive enantiomer is clearly wasteful. Thus using the single enantiomer (isomer or eutomer) should enable the dose of the drug to be lowered, reduce the interpatient variability in the response and, hopefully, reduce the side effects and toxicity of the drug.
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