Formation of active metabolites of psychotropic drugs. An updated review of their significance

Clin Pharmacokinet. 1990 Jun;18(6):434-59. doi: 10.2165/00003088-199018060-00002.

Abstract

Most of the currently available psychotropic drugs form 1 or more active metabolites during in vivo biotransformation in humans and/or animals. In some cases these metabolites are rapidly conjugated and excreted, but in others they attain blood and/or brain concentrations within the same range as, or even higher than, those of the parent drug, thus being potential biologically active compounds. The formation of metabolites with their own biological activity in addition to that of the parent compound may result in a complex situation where different chemical species participate in the final effects. These chemical species may have different pharmacokinetic properties of distribution and clearance. They may act by similar mechanisms, by different mechanisms or even antagonistically. The formation of active metabolites may be important not only for the therapeutic outcome but also for explaining the toxicity of particular drugs. The examples given, although limited, provide evidence that studies on drug metabolites are essential for an understanding of the mechanism of action of psychotropic drugs, and for extrapolating pharmacological and toxicological findings from animals to humans. The development of any new psychotropic agent requires knowledge of the pharmacology and toxicology of all active species as well as their pharmacokinetic profile, including the extent to which they reach the central nervous system.

Publication types

  • Review

MeSH terms

  • Animals
  • Biotransformation
  • Humans
  • Psychotropic Drugs / metabolism*
  • Psychotropic Drugs / pharmacology
  • Psychotropic Drugs / therapeutic use

Substances

  • Psychotropic Drugs