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Enantiomers eudismic ratio

Receptor Tissue Eutomer pA2 (enantiomer) Eudismic ratio... [Pg.157]

It is common to call the most active enantiomer eutomer and the less active one distomer. The ratio of the pharmacological activity of these are called the eudismic ratio (ER) and Pfeiffer s mle states that the lower the effective dose of a drug the greater the difference in the pharmacological effect of the optical isomers . When two enantiometic... [Pg.20]

The more active isomer (where activity refers to binding affinity at a defined receptor) is designated the eutomer, the less active is the distomer. The ratio of activities is the eudismic ratio, and its logarithm, the eudismic index, is then proportional to the difference in binding free energy between the enantiomers. The eudismic index is a quantitative measure of chiral discrimination. [Pg.89]

It is important to introduce two other terms that compare the pharmacological activity of a pair of enantiomers. The isomer imparting the desired activity is called the eu-tomer (in the case of Thalidomide this is the R-enantiomer), whereas the isomer which is inactive or causes unwanted side effects is called the distomer (this is the S-enantiomer for Thalidomide). Comparison of the potencies of the two isomers comes from the eudismic ratio and this can be used in vitro or in vivo. [Pg.785]

CF3CH20 An example of a lack of stereoselectivity of pharmacological action. The enantiomers of flecainide demonstrates an eudismic ratio... [Pg.2151]

The (+)-cis isomer of (108) was the most potent muscarinic of the series. It demonstrated a eudismic ratio of the same high order of magnitude as that for muscarine and the dioxolanes. This (+)-cis enantiomer has the same absolute configuration as the muscarini-cally most active L-(+)-muscarine (2) and the (+)-cis-dioxolane (109). The other isomers represented by structure (108), although much less potent than the (+)-cis isomer, also demonstrated a degree of muscarinic agonist effect. All four isomers of structure (108) showed similar nicotinic potency and activity, close to that of carbamyl choline, and eudismic ratios were small. [Pg.59]

Compound (110) is exponentially less potent than (11 l)at muscarinic receptors. Both compounds demonstrate low nicotinic potency and activity. The sulfone congeners (112) of the enantiomers (212,5JR and 2S,5S) of the cis-structure are weak muscarinics with a eudismic ratios of unity. [Pg.59]

Shortening of the aminopropyl to an aminoethyl chain in the eutomers of the HHD-deriva-tives (3->8, 4->9, 6- ll) did not change significantly the affinities. In contrast, the stereoselectivity ratios for the enantiomers of these aminopropyl/aminoethyl pairs were changed. It was found, that the stereoselectivity ratios for 3 (aminopropyl series) were higher than those for the related compound in the aminoethyl series (8). Vice versa, the amide of the HHD type (6) exhibited lower eudismic ratios than the amide of the THP type (11). [Pg.59]

Similarly to the trend observed at aj -adrenoreceptors, stereoisomers (-)-31, (-l-)-31, (-)-32 and ( + )-32 displayed a radioreceptor binding affinity higher than that observed in functional assays at 5-HT, receptors. Furthermore, the eudismic ratio between (-)-31 and ( + )-31 enantiomers was identical to that observed in functional assays whereas for (- )-32 and (-I- )-32 it was much lower. However, a difference in potency observed for the agonists... [Pg.119]

Stereoselectivity was defined by Rauws ° as follows Stereoselectivity is the extent to which an enzyme or other macromolecule, or tnacromolecular structure (antibody or receptor) exhibits affinity towards one molecule of a pair of isomers in comparison with and in contrast to the other isomer. Lehmann has expressed this in a mathematical form the ratio of activity of the better fitting enantiomer (eutomer, Greek, eu = good), to that of the less fitting enantiomer (distomer Greek, dys = ba(i) is defined eudismic ratio. From this a eudismic affinity quotient can be derived (Table 17.3). [Pg.278]

One usually admits that the discriminative effect between the two enantiomers increases with the proximity of the chiral centre to the site of interaction with the receptor. An empirical rule published by Pfeiffer in 1956 states that the isomeric activity ratio (eudismic ratio) of a highly active... [Pg.279]

The activity of the racemic trans ( ) compound in vitro as well as in vivo is caused by McN 5652-Z its trans (+) enantiomer as the trans (-) enantiomer is comparatively inactive. The eudismic ratio for 5-HT uptake inhibition (Kj trans (-) / K trans (+)) is 150 and for NE uptake inhibition 155. The selectivity index of the trans (+) isomer for 5-HT upteike inhibition versus NE uptake inhibition (K NE / Kj 5-HT) is a moderate 4.6. [Pg.351]

For example, initial investigations on the effect of the enantiomers of isoprenaline on blood pressure in cats and dogs yielded values for the eudismic ratio (—)/(+) of 11.8 and 87.5, respectively, whereas later studies yielded ratios of 1000 and 450 [18,43]. The authors pointed out that purification to constant biological activity was a better criterion for enantiomeric purity than constant specific rotation or melting point [43], an argument confirmed by subsequent investigations by Barlow, who indicated the significance of trace quantities of enantiomeric impurities on the eudismic ratio. The interested reader should refer to the articles of Barlow [44] and Barlow et al. [45] for further details. [Pg.158]

The most important differences between enantiomers occur in drug receptor interactions. Indeed, Lehmann [34] has stated, the stereoselectivity displayed by pharmacological systems constitutes the best evidence that receptors exist and that they incorporate concrete molecular entities as integral components of their active-sites. In contrast to the pharmacokinetic properties of a pair of enantiomers (Sec. 4), differences in pharmacodynamic activity tend to be more marked, and eudismic ratios of 100 to 1000 are not uncommon. [Pg.159]

In the case of fluoxetine (Fig. 11), the individual enantiomers have similar potency in vitro in terms of the inhibition of 5-hydroxytryptamine (5-HT) uptake, with eudismic ratios varying between 1.1 and 1.9 depending on the test system used [78]. The inhibition of 5-HT reuptake lasted up to 24 hours and 8 hours following administration of ( )- and (7 )-fluoxetine, respectively, to the rat. However, the difference in duration is probably associated with demethylation to norfluoxetine as the 5-enantiomer of the metabolite is approximately 15-fold more potent than (7 )-norfluoxetine as... [Pg.165]

A number of studies have indicated the greater potency of (eudismic ratio between 130 and 160 [84,85]. As with fluoxetine, demethylation yields an active metaboHte, desmethylcitalopram, which in the case of the -enantiomer is approximately 6.7-fold less potent than the drug, but the eudismic ratio (S/R) decreases to 6.5. In this instance, the 7 -enantiomer of the metabolite is approximately fourfold more potent than (7 )-citalopram [84]. Following administration of the racemate to patients, the plasma concentrations of the 5-enantiomer are approximately one-third of those of the total drug, with a mean S/R ratio of 0.56 [86]. The single 5-enantiomer, given the generic name escitalopram, has been marketed since 2002. [Pg.167]

Example 4.18 Fluoxetine (Prozac) TM 4.15 is a well-known antidepressive, an inhibitor of serotonin uptake in the nerve cells. This chiral drug is introduced in therapy as a racemate since numerous biological and pharmacological studies have confirmed that the eudismic ratio for fluoxetine enantiomers is near unity. The eudismic ratio is the ratio of the biological activity of enantiomers, formerly denoted as eutomers (more active) and distomers, less active or inactive enantiomers. [Pg.94]

With respect to their relative affinities to a chiral binding site, all different pairs of enantiomers differ more or less in their relative affinities. Eudismic ratios, i.e., the ratio of the affinity or biological activity of the more active analog (the eutomer) to the less active one (the distomer) between 1 and 500000 have been observed (e.g.. Refs. 3, 25, 26). [Pg.452]

Stereoisomerism arises from the occurrence within drug molecules of chiral centres. The number of possible stereoisomers is 2", where n is the number (usually unity) of chiral centres. A substantial proportion of the commonly used synthetic drugs contain one or more chiral centres and are commercially available as preparations (dosage forms) containing racemates. Drug preparations containing racemic mixtures have been described as combinations of active drug plus isomeric ballast when one enantiomer produces little or no therapeutic effect (Ariens, 1986). The eudismic or potency ratio is defined as the ratio of the doses (in vivo studies) or the concentrations (in vitro studies)... [Pg.164]


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Enantiomers ratio

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