ArticleBritish journal of pharmacology2016
The G-protein biased partial κ opioid receptor agonist 6'-GNTI blocks hippocampal paroxysmal discharges without inducing aversion.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Characterization of the intrahippocampal kainic acid model in female mice with a special focus on seizure suppression by antiseizure medications.Experimental neurology · 2024Article
- Structure-function relationship of dynorphin B variants using naturally occurring amino acid substitutions.Frontiers in pharmacology · 2024Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- Opioids, microglia, and temporal lobe epilepsy.Frontiers in neurology · 2023Review
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.Pharmacological research · 2022Review
- Kappa Opioid Receptor Ligands and Pharmacology: Diphenethylamines, a Class of Structurally Distinct, Selective Kappa Opioid Ligands.Handbook of experimental pharmacology · 2022Review
- The Kappa Opioid Receptor System in Temporal Lobe Epilepsy.Handbook of experimental pharmacology · 2022Article
- Development of Diphenethylamines as Selective Kappa Opioid Receptor Ligands and Their Pharmacological Activities.Molecules (Basel, Switzerland) · 2020Review
- Strategies for DevelopingThe Journal of pharmacology and experimental therapeutics · 2020Review
- Biased Opioid Ligands.Molecules (Basel, Switzerland) · 2020Review
- Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain.Frontiers in neuroscience · 2020Article
- Bulleyaconitine A Inhibits Visceral Nociception and Spinal Synaptic Plasticity through Stimulation of Microglial Release of Dynorphin A.Neural plasticity · 2020Article
- Dynorphin-based "release on demand" gene therapy for drug-resistant temporal lobe epilepsy.EMBO molecular medicine · 2019Article
- A Review of the Therapeutic Potential of Recently Developed G Protein-Biased Kappa Agonists.Frontiers in pharmacology · 2019Review
- G protein signaling-biased agonism at the κ-opioid receptor is maintained in striatal neurons.Science signaling · 2018Article
- In vivo brain GPCR signaling elucidated by phosphoproteomics.Science (New York, N.Y.) · 2018Article
- Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics?Drug discovery today · 2017Review
- Selective κ receptor partial agonist HS666 produces potent antinociception without inducing aversion after i.c.v. administration in mice.British journal of pharmacology · 2017Article
- The Opioid System in Temporal Lobe Epilepsy: Functional Role and Therapeutic Potential.Frontiers in molecular neuroscience · 2017Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeWith a prevalence of 1-2%, epilepsies belong to the most frequent neurological diseases worldwide. Although antiepileptic drugs are available since several decades, the incidence of patients that are refractory to medication is still over 30%. Antiepileptic effects of κ opioid receptor (κ receptor) agonists have been proposed since the 1980s. However, their clinical use was hampered by dysphoric side effects. Recently, G-protein biased κ receptor agonists were developed, suggesting reduced aversive effects. EXPERIMENTAL APPROACH: We investigated the effects of the κ receptor agonist U-50488H and the G-protein biased partial κ receptor agonist 6'-GNTI in models of acute seizures and drug-resistant temporal lobe epilepsy and in the conditioned place avoidance (CPA) test. Moreover, we performed slice electrophysiology to understand the functional mechanisms of 6'-GNTI. KEY
resultsAs previously shown for U-50488H, 6'-GNTI markedly increased the threshold for pentylenetetrazole-induced seizures. All treated mice displayed reduced paroxysmal activity in response to U-50488H (20 mg·kg(-1) ) or 6'-GNTI (10-30 nmoles) treatment in the mouse model of intra-hippocampal injection of kainic acid. Single cell recordings on hippocampal pyramidal cells revealed enhanced inhibitory signalling as potential mechanisms causing the reduction of paroxysmal activity. Effects of 6'-GNTI were blocked in both seizure models by the κ receptor antagonist 5'-GNTI. Moreover, 6'-GNTI did not induce CPA, a measure of aversive effects, while U-50488H did. CONCLUSIONS AND IMPLICATIONS: Our data provide the proof of principle that anticonvulsant/antiseizure and aversive effects of κ receptor activation can be pharmacologically separated in vivo.
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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.