Abstract
The National Institute of Mental Health (NIMH) Psychoactive Drug Screening Program (PDSP) is a resource that provides free screening of novel compounds to academic investigators. This program differs from other public-sector screening programs in that compounds are screened against a large panel of transmembrane receptors, channels, and transporters, a selection that currently includes a large portion of the whole neuro-receptorome. This review discusses the research areas that can profit from this resource, exemplified by recent findings. The first area is the identification of side effects of medications. Examples include the identification of the histamine H1 receptor as being responsible for weight gain under antipsychotic treatment and the association of 5-HT2B receptor agonism with cardiac valvulopathy, which led to the removal of several medications. A second area is the identification of mechanisms of actions of medications and natural products. Examples are the finding that the kappa opioid receptor is the pharmacological target of the potent hallucinogen salvinorin A, that ephedrine and related compounds are not acting through direct sympathomimetic action, the identification of a strong dopaminergic action of WAY-100635, a compound that had been used as a selective 5-HT1A antagonist, and the discovery that the metabolite desmethylclozapine activates M1 muscarinic receptors, an activity that might contribute to the clinical efficacy of the antipsychotic drug clozapine. A third, relatively new area is the identification of inert compounds as agonists for engineered designer receptors that no longer respond to their natural ligand (DREADDs) but exhibit unchanged signaling properties.
Keywords: G protein-coupled receptors, GPCR, receptorome, screening, PDSP
Combinatorial Chemistry & High Throughput Screening
Title: Massively Parallel Screening of the Receptorome
Volume: 11 Issue: 6
Author(s): Niels H. Jensen and Bryan L. Roth
Affiliation:
Keywords: G protein-coupled receptors, GPCR, receptorome, screening, PDSP
Abstract: The National Institute of Mental Health (NIMH) Psychoactive Drug Screening Program (PDSP) is a resource that provides free screening of novel compounds to academic investigators. This program differs from other public-sector screening programs in that compounds are screened against a large panel of transmembrane receptors, channels, and transporters, a selection that currently includes a large portion of the whole neuro-receptorome. This review discusses the research areas that can profit from this resource, exemplified by recent findings. The first area is the identification of side effects of medications. Examples include the identification of the histamine H1 receptor as being responsible for weight gain under antipsychotic treatment and the association of 5-HT2B receptor agonism with cardiac valvulopathy, which led to the removal of several medications. A second area is the identification of mechanisms of actions of medications and natural products. Examples are the finding that the kappa opioid receptor is the pharmacological target of the potent hallucinogen salvinorin A, that ephedrine and related compounds are not acting through direct sympathomimetic action, the identification of a strong dopaminergic action of WAY-100635, a compound that had been used as a selective 5-HT1A antagonist, and the discovery that the metabolite desmethylclozapine activates M1 muscarinic receptors, an activity that might contribute to the clinical efficacy of the antipsychotic drug clozapine. A third, relatively new area is the identification of inert compounds as agonists for engineered designer receptors that no longer respond to their natural ligand (DREADDs) but exhibit unchanged signaling properties.
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Cite this article as:
Jensen H. Niels and Roth L. Bryan, Massively Parallel Screening of the Receptorome, Combinatorial Chemistry & High Throughput Screening 2008; 11 (6) . https://dx.doi.org/10.2174/138620708784911483
DOI https://dx.doi.org/10.2174/138620708784911483 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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