ReviewBiological psychiatry2012
Psychiatric drugs bind to classical targets within early exocytotic pathways: therapeutic effects.
Review in Biological psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- Ketamine persists within neuronal compartments long after systemic clearance.Research square · 2026Article
- The Oxytocin Receptor in Spermatozoa May Originate From Both Spermatogenesis and Epididymal Maturation, and Regulates Capacitation.Andrology · 2026Article
- Potential Protective Effects of Pungent Flavor Components in Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2024Review
- Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.Translational psychiatry · 2024Article
- Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Beyond "Psychotropic": Repurposing Psychiatric Drugs for COVID-19, Alzheimer's Disease, and Cancer.The Journal of clinical psychiatry · 2023Review
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors.Science (New York, N.Y.) · 2023Article
- SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids.Translational psychiatry · 2023Article
- Fluorescence Screens for Identifying Central Nervous System-Acting Drug-Biosensor Pairs for Subcellular and Supracellular Pharmacokinetics.Bio-protocol · 2022Article
- Three Mutations Convert the Selectivity of a Protein Sensor from Nicotinic Agonists to S-Methadone for Use in Cells, Organelles, and Biofluids.Journal of the American Chemical Society · 2022Article
- Biophysical characterization of lynx-nicotinic receptor interactions using atomic force microscopy.FASEB bioAdvances · 2021Article
- The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans.Molecular psychiatry · 2021Article
- The physiology of regulated BDNF release.Cell and tissue research · 2020Review
- Modulation of cholinergic activity through lynx prototoxins: Implications for cognition and anxiety regulation.Neuropharmacology · 2020Review
- Cocaine engages a non-canonical, dopamine-independent, mechanism that controls neuronal excitability in the nucleus accumbens.Molecular psychiatry · 2020Article
- Location and Cell-Type-Specific Bias of Metabotropic Glutamate Receptor, mGluACS chemical neuroscience · 2019Article
- Determining the pharmacokinetics of nicotinic drugs in the endoplasmic reticulum using biosensors.The Journal of general physiology · 2019Article
- Non-canonical Targets Mediating the Action of Drugs of Abuse: Cocaine at the Sigma-1 Receptor as an Example.Frontiers in neuroscience · 2019Article
- Biosensors Show the Pharmacokinetics of S-Ketamine in the Endoplasmic Reticulum.Frontiers in cellular neuroscience · 2019Article
- Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The classical targets for antipsychotic and antidepressant drugs are G protein-coupled receptors and neurotransmitter transporters, respectively. Full therapeutic actions of these drugs require several weeks. We show how therapeutic effects may eventually accrue after existing therapeutic ligands bind to these classical targets, not on the plasma membrane but rather within endoplasmic reticulum (ER) and cis-Golgi. Consequences of such binding may include pharmacological chaperoning: the nascent drug targets are stabilized against degradation and can therefore exit the ER more readily. Another effect may be matchmaking: heterodimers and homodimers of the target form and can more readily exit the ER. Summarizing recent data for nicotinic receptors, we explain how such effects could lead to reduced ER stress and to a decreased unfolded protein response, including changes in gene activation and protein synthesis. In effects not directly related to cellular stress, escorting would allow increased ER exit and trafficking of known associated proteins, as well as other proteins such as growth factors and their receptors, producing both cell-autonomous and non-cell-autonomous effects. Axonal transport of relevant proteins may underlie the several weeks required for full therapy. In contrast, the antidepressant effects of ketamine and other N-methyl-D-aspartate receptor ligands, which occur within <2 hours, could arise from dendritically localized intracellular binding, followed by chaperoning, matchmaking, escorting, and reduced ER stress. Thus, the effects of intracellular binding extend beyond proteostasis of the targets themselves and involve pathways distinct from ion channel and G protein activation. We propose experimental tests and note pathophysiological correlates.
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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.