Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery

Pharmacol Ther. 2004 May;102(2):99-110. doi: 10.1016/j.pharmthera.2004.03.004.


Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at the "receptorome" (that portion of the proteome encoding receptors). An overview of the receptorome is given and various in silico, public-domain resources are described. Newly developed tools for the in silico mining of data derived from the National Institute of Mental Health Psychoactive Drug Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail. Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System / drug effects
  • Drug Delivery Systems / methods*
  • Drug Evaluation, Preclinical / methods*
  • Humans
  • Membrane Proteins / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification*
  • Plant Extracts / pharmacology
  • Plants, Medicinal / chemistry
  • Plants, Medicinal / classification
  • Psychotropic Drugs / chemistry
  • Psychotropic Drugs / isolation & purification*
  • Psychotropic Drugs / pharmacology


  • Membrane Proteins
  • Plant Extracts
  • Psychotropic Drugs