Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia

By Bryan L. Roth, Douglas J. Sheffler, W. Kroeze. Nature reviews. Drug discovery, 2004

1,132 citations recorded by the source corpus.

Subfields: Biological Psychiatry, Molecular Biology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/34c3b64956cf938e8d4600790365c37c7d9d3ce0

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Citations in the corpus

Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference (2012, background): “For example, serotonin and serotonergic drugs not only bind to G protein-coupled receptors (GPCRs) such as 5-hydroxytryptamine receptors 1, 2 and 4–7 (5-HT 1,2,4–7 ), but also might bind to an ion channel, i.e. 5-HT 3 [2,3].”
Network pharmacology: the next paradigm in drug discovery. (2008, background): “As increased understanding of the role of networks in the robustness and redundancy of biological systems challenges the dominant assumption of single target drug discover”
Predicting drug-target interactions using restricted Boltzmann machines (2013, background): “…example, serotonin and serotonergic drugs can interact with both 5-HT G protein-coupled receptors and 59HT 3A ion channel proteins, even though these two target proteins are not related in sequence or structure (Cheng et al ., 2012; Keiser et al ., 2007; Kroeze et al ., 2002; Roth et al ., 2004).”
STRUCTURE OF THE D2 DOPAMINE RECEPTOR BOUND TO THE ATYPICAL ANTIPSYCHOTIC DRUG RISPERIDONE (2018, background): “(4) Finally, an outward movement of the extracellular tip of TM VII (Fig.”
Relating protein pharmacology by ligand chemistry (2007, background): “(iii) Detailed view of ionotropic (5-HT3) serotonergics: 5-HT4 agonists (1), 5-HT4 antagonists (2), 5-HT2 antagonists (3), 5-HT3 antagonists (4), and 5-HT3 agonists (5).”
5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology (2018, positive): “…shotguns’’) are frequently more effective therapeutics (Roth et al., 2004), as exemplified by the atypical antipsychotics clozapine (Clozaril) and aripiprazole (Abilify), which interact with numerous GPCRs (Jacobson et al., 2014; McCorvy and Roth, 2015; Roth et al., 2004; Shapiro et al., 2003).”
The Physiology, Signaling, and Pharmacology of Dopamine Receptors (2011, background): “The fact that essentially all clinically effective antipsychotics possess the ability to block D2 dopamine receptors indicates that D2 dopamine receptors are likely to play a critical role in the psychotic reactions observed in schizophrenia and bipolar disorder (Snyder et al., 1970; Roth et al., 20”
Functional Selectivity and Classical Concepts of Quantitative Pharmacology (2007, background): “Although modern drug discovery recently has recognized that there is value in ligands that act by simultaneously targeting multiple receptors (Roth et al., 2004), there is still the widespread view that the characteristics of ligands at target receptors can be described by their “intrinsic efficacy””
Global mapping of pharmacological space (2006, background): “The concept of relating proteins in chemical space by polypharmacology interactions provides the foundation for a ligand-based protein classification and valuable resource for understanding the molecular basis for compound promiscuit”
Targeted drug delivery to tumors: Myths, reality and possibility (2011, neutral): “(If a drug is chosen to interact with multiple targets by design, it is can be considered as a “magic shotgun” [66]).”