ArticleProceedings of the National Academy of Sciences of the United States of America1997
Substitution of a mutant alpha2a-adrenergic receptor via "hit and run" gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 363 citations in OpenAlex.
- Effect of single-dose dexmedetomidine on postoperative recovery after ambulatory ureteroscopy and ureteric stenting: a double blind randomized controlled study.BMC anesthesiology · 2018Trial
- A Review of Alpha-2 Adrenergic Agents Implicated in Opioid Use Disorder.ACS chemical neuroscience · 2026Review
- The locus coeruleus maintains core body temperature and protects against hypothermia during dexmedetomidine-induced sedation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Discovery and development of an oral analgesic targeting the α2B adrenoceptor.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dexmedetomidine directly binds to and inhibits Toll-like receptor 4.International immunopharmacology · 2024Article
- The Discovery of Novel αInternational journal of molecular sciences · 2024Article
- Noradrenaline depresses facial stimulation-evoked cerebellar MLI-PC synaptic transmission via α2-AR/PKA signaling cascade in vivo in mice.Scientific reports · 2023Article
- Design, Synthesis, and Bioevaluation of Dexmedetomidine Prodrug.ACS medicinal chemistry letters · 2023Article
- Alpha2-Adrenergic Receptors as a Pharmacological Target for Spike-Wave Epilepsy.International journal of molecular sciences · 2023Review
- Sedative Properties of Dexmedetomidine Are Mediated Independently from Native Thalamic Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel Function at Clinically Relevant Concentrations.International journal of molecular sciences · 2022Article
- Structure-based discovery of nonopioid analgesics acting through the αScience (New York, N.Y.) · 2022Article
- Characterization of Chicken αGenes · 2022Article
- Spike-Dependent Dynamic Partitioning of the Locus Coeruleus Network through Noradrenergic Volume Release in a Simulation of the Nucleus Core.Brain sciences · 2022Article
- Recommended doses of medetomidine-midazolam-butorphanol with atipamezole for preventing hypothermia in mice.The Journal of veterinary medical science · 2022Article
- The Inert Brain: Explaining Neural Inertia as Post-anaesthetic Sleep Inertia.Frontiers in neuroscience · 2021Article
- D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in Rats.Frontiers in pharmacology · 2021Article
- Effects on the Upper Airway Morphology with Intravenous Addition of Ketamine after Dexmedetomidine Administration in Normal Children.Journal of clinical medicine · 2020Article
- A Guide to Understanding "State-of-the-Art" Basic Research Techniques in Anesthesiology.Anesthesia and analgesia · 2020Review
- Activation of the αNature chemical biology · 2020Article
- Azi-medetomidine: Synthesis and Characterization of a Novel α2 Adrenergic Photoaffinity Ligand.ACS chemical neuroscience · 2019Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Norepinephrine contributes to antinociceptive, sedative, and sympatholytic responses in vivo, and alpha2 adrenergic receptor (alpha2AR) agonists are used clinically to mimic these effects. Lack of subtype-specific agonists has prevented elucidation of the role that each alpha2AR subtype (alpha2A, alpha2B, and alpha2C) plays in these central effects. Here we demonstrate that alpha2AR agonist-elicited sedative, anesthetic-sparing, and analgesic responses are lost in a mouse line expressing a subtly mutated alpha2AAR, D79N alpha2AAR, created by two-step homologous recombination. These functional changes are accompanied by failure of the D79N alpha2AAR to inhibit voltage-gated Ca2+ currents and spontaneous neuronal firing, a measure of K+ current activation. These results provide definitive evidence that the alpha2AAR subtype is the primary mediator of clinically important central actions of alpha2AR agonists and suggest that the D79N alpha2AAR mouse may serve as a model for exploring other possible alpha2AAR functions in vivo.
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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.