Enantiomers' potential in psychopharmacology--a critical analysis with special emphasis on the antidepressant escitalopram.
Stereochemistry is now influencing most areas of pharmacotherapy, with a growing awareness in the field of psychiatry and, more specifically, depression. This is due to the fact that the enantiomers of many chiral drugs may have distinct pharmacological, pharmacokinetic and/or pharmacogenetic profiles. Consequently, in some instances there may be an advantage in using a single enantiomer over the racemic form-thus providing a basis for the development of new therapeutic agents, as well as the potential to improve current treatments. This review highlights some of the potential advantages and disadvantages that using single enantiomers might offer. The principles are exemplified through reference to the stereoselective properties of several established chiral psychotropic drugs, including thioridazine, methadone, trimipramine, mianserin, mirtazapine, fluoxetine and citalopram. Emphasis is given to the treatment of depression and how the potential of one pure enantiomer-escitalopram, the S-enantiomer of the selective serotonin reuptake inhibitor citalopram-appears to be fulfilling its preclinical promise in the clinic.
Département Universitaire de Psychiatrie Adulte, Unité de Biochimie et Psychopharmacologie Clinique, Hôpitalde Cery, CH-1008, Prilly-Lausanne, Switzerland. pierre.baumann@inst.hospvd.ch
Pierre
P
Baumann
Daniele F
DF
Zullino
Chin B
CB
Eap
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015283:Citalopram / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy; D005473:Fluoxetine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy; D008803:Mianserin / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D015394:Molecular Structure; D011619:Psychotropic Drugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013237:Stereoisomerism; D013881:Thioridazine / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014299:Trimipramine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D005473:Fluoxetine; D008803:Mianserin; D011619:Psychotropic Drugs; D017367:Selective Serotonin Reuptake Inhibitors; D013881:Thioridazine; D014299:Trimipramine