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

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 elucidat...

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Bibliographic Details
Published in:Pharmacology & therapeutics (Oxford) 2004-05, Vol.102 (2), p.99-110
Main Authors: Roth, Bryan L, Lopez, Estela, Beischel, Scott, Westkaemper, Richard B, Evans, Jon M
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0163-7258
DOI:10.1016/j.pharmthera.2004.03.004