Stereochemistry and drug efficacy and development: relevance of chirality to antidepressant and antipsychotic drugs
Why this work is in the frame
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Bibliographic record
Abstract
Many drugs contain a chiral center or a center of unsaturation, or such centers result during metabolism of these drugs. Often such drugs are marketed as a mixture of the resultant enantiomers (racemates) or of geometric isomers, respectively. These enantiomers (molecules that are not superimposible on their mirror image) or geometric isomers may differ markedly from each other with regard to their pharmacodynamic and/or pharmacokinetic properties. This review deals primarily with drugs with chiral centers, and possible complications arising from the use of racemates are discussed. Recent developments in resolution of enantiomers, increased knowledge of the molecular structure of specific drug targets and a heightened awareness of several possible advantages of using single enantiomers rather than racemic mixtures of drugs have led to an increased emphasis on understanding the role of chirality in drug development. This has resulted in increased investigation of individual enantiomers early on in the development of drugs and in 'chiral switching', i.e. the replacement of a racemate of a drug which has already been approved or marketed by a single enantiomer. Although stereochemistry is an important matter to consider in drugs of virtually all classes, this review focuses on the relevance of chirality to antidepressant and antipsychotic drugs. Examples of the effects of chiral centers on the properties of antidepressants (tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, viloxazine, bupropion, mianserin, venlafaxine, mirtazapine and reboxetine), antipsychotics and/or some of their metabolites are discussed.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it