Enantiomers receptor site

The difference m odor between (R) and (S) carvone results from their different behavior toward receptor sites m the nose It is believed that volatile molecules occupy only those odor receptors that have the proper shape to accommodate them Because the receptor sites are themselves chiral one enantiomer may fit one kind of receptor while the other enantiomer fits a different kind An analogy that can be drawn is to hands and gloves Your left hand and your right hand are enantiomers You can place your left hand into a left glove but not into a right one The receptor (the glove) can accommodate one enantiomer of a chiral object (your hand) but not the other... 

Section 7 8 Both enantiomers of the same substance are identical m most of then-physical properties The most prominent differences are biological ones such as taste and odor m which the substance interacts with a chiral receptor site m a living system Enantiomers also have important conse quences m medicine m which the two enantiomeric forms of a drug can have much different effects on a patient... 

The fact that the enantiomers of a compound do not smell the same suggests that the receptor sites in the nose for these compounds are chiral, and only the correct enantiomer will fit its particular site (just as a hand requires a glove of the ocrrect chirality for a proper fit). 

Zopiclone is widely used as a sedative-hypnotic. It is metabolized to an inactive N-desmethylated derivative and an active N-oxide compound, both of which contain chiral centres. S-Zopiclone has a 50-fold higher affinity for the benzodiazepine receptor site than the R-enantiomer. This could be therapeutically important, particularly if the formation and the urinary excretion of the active metabolite benefits the S-isomer, which appears to be the case. As the half-life of the R-enantiomer is longer than that of the S-form, it would seem advantageous to use the R-isomer in order to avoid the possibility of daytime sedation and hangover effects which commonly occur with long-acting benzodiazepine receptor agonists. 

The more active enantiomer at one type of receptor site may not be more active at another receptor type, eg, a type that may be responsible for some other effect. For example, carvedilol, a drug that interacts with adrenoceptors, has a single chiral center and thus two enantiomers (Figure 1-2, Table 1-1). One of these enantiomers, the (S) -) isomer, is a potent B-receptor blocker. The (R)(+) isomer is 100-fold weaker at the receptor. However, the isomers are approximately equipotent as -receptor blockers. Ketamine is an intravenous anesthetic. The (+) enantiomer is a more potent anesthetic and is less toxic than the (-) enantiomer. Unfortunately, the drug is still used as the racemic mixture. 

Answer Only one of the two enantiomers of the drug molecule (which has a chiral center) is physiologically active, for reasons described in the answer to Problem 3 (interaction with a stereospecific receptor site). Dexedrine, as manufactured, consists of the single enantiomer (D-amphetamine) recognized by the receptor site. Benzedrine was a racemic mixture (equal amounts of D and l isomers), so a much larger dose was required to obtain the same effect. 

A chiral substance is enantiopure or homochiral when only one of two possible enantiomers is present. A chiral substance is enantioenriched or heterochiral when an excess of one enantiomer is present but not to the exclusion of the other. If the desired product is an enantiomer, the reaction needs to be sufficiently stereoselective even when atom economy is 100%. For the biological usage we almost need one enantiomer and in high purity. This is because when biologically active chiral compounds interact with its receptor site which is chiral, the two enantiomers of the chiral molecule interact differently and can lead to different chemistry. For example, one enantiomer of asparagines (1.37) is bitter while the other is sweet. As far as medicinal applications are concerned, a given enantiomer of a drug may be effective while the other is inactive or potentially harmful. For example, one enantiomer of ethanbutol (1.38) is used as antibiotic and the other causes blindness. 

However, the studies on the calcium channel blockers remained centered even today around the l,4-dihydropyridine class. Since this class of compounds can also act as calcium channel activators, attention has always been drawn towards their structure-activity relationship studies. Attempts were made to differentiate in the mechanisms of their agonist and antagonist activities. On the basis of the force field and quantum mechanical calculations, Holtze and Marrer [51] discovered a imique area of the molecular potentials where Ca agonists and antagonists possess potential of opposite sign. These authors demonstrated that the molecular potential of a simple receptor site was reduced by interaction with calciiun channel activators and, on the contrary, increased by interaction with calcium channel blockers. These opposite effects probably could be the basis for the opposite actions of DHP enantiomers at the potential-dependent calcium channel. 

At high doses (R)-(92) selectively stimulated presynaptic dopaminergic receptor sites, whereas at lower doses it selectively stimulated postsynaptic receptor sites (59). In contrast, the ( S)-enantiomer stimulated presynaptic dopamine receptors and at the same dose level, it blocked postsynaptic dopamine recep-... 

Q8. (-)-Carvone (73) occurs in spearmint and its enantiomer (+)-carvone (74) is found in caraway seed. To the human sense of smell, these two enantiomers have different odours. Where is the stereogenic centre in 73 and in 74 What conclusions can be drawn about the human olfactory receptor site ... 

A. That different enantiomers 73 and 74 give rise to distinct odours means that the olfactory receptor site in humans is chiral. This has the consequence that the interactions of the enantiomers with the receptor site are diastereomeric and accordingly different odours are perceived. There are many pairs of enantiomers whose odour is identical, but differences between odours of enantiomers are most common in cyclic compounds (see Pybus and Sell16). The stereo-genic centre in both 73 and 74 is at C(5). 

The molecule has a single chiral centre and when the molecule is drawn in the same manner as morphine, we would expect the R enantiomer to be the more active enantiomer. This proves to be the case with the R enantiomer being twice as powerful as morphine, whereas the 5 enantiomer is inactive. This is quite a dramatic difference. Since the R and 5 enantiomers have identical physical properties and lipid solubility, they should both reach the receptor site to the same extent, and so the difference in activity is most probably due to receptor-substrate interactions. 

The biological response induced by a pair of enantiomers can differ in potency (quantitative difference) or in nature (qualitative difference). In the latter case, it is assumed that one enantiomer acts at one receptor site, whereas its antipode is recognized by other sites and possesses a different activity and toxicity profile. 

Two optical isomers are never antagonists, at least at comparable dosages. This comes from the space relationship required for the interaction with the receptor site which is only slightly altered by passing from S to R forms, or vice-versa. If one of the enantiomers achieves the optimal... 

Advances in industrial chemical processes have allowed pharmaceutical manufacturers to take drugs that were originally marketed in racemic form and divide them into individual enantiomers, each of which may have unique properties. For some drugs, such as zopiclone, only one enantiomer (eszopiclone) is active the FDA has allowed such once-generic drugs to be patented and marketed under another name. In other cases, such as ibuprofen, both enantiomers produce the same effects. Steroid receptor sites also show stereoisomer specificity. 

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