ArticleACS chemical biology2016
ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Mapping the Ligand-dependent Remodeling of the Conformational Entropy Landscape in Neurotensin Receptor 1 by NMR-guided Molecular Simulations.bioRxiv : the preprint server for biology · 2026Article
- Biased Allosteric Modulation in GPCR Drug Discovery.Handbook of experimental pharmacology · 2026Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Development of a Fluorescent Ligand for the Intracellular Allosteric Binding Site of the Neurotensin Receptor 1.ACS pharmacology & translational science · 2024Article
- Platelet Activation Pathways Controlling Reversible Integrin αIIbβ3 Activation.TH open : companion journal to thrombosis and haemostasis · 2024Article
- Neurotensin and Neurotensin Receptors in Stress-related Disorders: Pathophysiology & Novel Drug Targets.Current neuropharmacology · 2024Review
- Neurotensin receptor 1-biased ligand attenuates neurotensin-mediated excitation of ventral tegmental area dopamine neurons and dopamine release in the nucleus accumbens.Neuropharmacology · 2023Article
- G protein-coupled receptors as targets for transformative neuropsychiatric therapeutics.American journal of physiology. Cell physiology · 2023Review
- Stabilization of pre-existing neurotensin receptor conformational states by β-arrestin-1 and the biased allosteric modulator ML314.Nature communications · 2023Article
- Neurotensin and Alcohol Use Disorders: Towards a Pharmacological Treatment.International journal of molecular sciences · 2023Review
- Ligands selectively tune the local and global motions of neurotensin receptor 1 (NTSCell reports · 2023Article
- Acute and protracted abstinence from methamphetamine bidirectionally changes intrinsic excitability of indirect pathway spiny projection neurons in the dorsomedial striatum.Scientific reports · 2022Article
- Discovery of a functionally selective ghrelin receptor (GHSRProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor.Journal of medicinal chemistry · 2022Review
- Visualization of real-time receptor endocytosis in dopamine neurons enabled by NTSR1-Venus knock-in mice.Frontiers in cellular neuroscience · 2022Article
- Bivalent ligands promote endosomal trafficking of the dopamine D3 receptor-neurotensin receptor 1 heterodimer.Communications biology · 2021Article
- Biased Allosteric Modulators: New Frontiers in GPCR Drug Discovery.Trends in pharmacological sciences · 2021Review
- β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.Cell · 2020Article
- Article
- A complex structure of arrestin-2 bound to a G protein-coupled receptor.Cell research · 2019Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Pharmacological treatment for methamphetamine addiction will provide important societal benefits. Neurotensin receptor NTR1 and dopamine receptor distributions coincide in brain areas regulating methamphetamine-associated reward, and neurotensin peptides produce behaviors opposing psychostimulants. Therefore, undesirable methamphetamine-associated activities should be treatable with druggable NTR1 agonists, but no such FDA-approved therapeutics exist. We address this limitation with proof-of-concept data for ML314, a small-molecule, brain penetrant, β-arrestin biased, NTR1 agonist. ML314 attenuates amphetamine-like hyperlocomotion in dopamine transporter knockout mice, and in C57BL/6J mice it attenuates methamphetamine-induced hyperlocomotion, potentiates the psychostimulant inhibitory effects of a ghrelin antagonist, and reduces methamphetamine-associated conditioned place preference. In rats, ML314 blocks methamphetamine self-administration. ML314 acts as an allosteric enhancer of endogenous neurotensin, unmasking stoichiometric numbers of hidden NTR1 binding sites in transfected-cell membranes or mouse striatal membranes, while additionally supporting NTR1 endocytosis in cells in the absence of NT peptide. These results indicate ML314 is a viable, preclinical lead for methamphetamine abuse treatment and support an allosteric model of G protein-coupled receptor signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.