Evidence map›Paper›PMID 27190170›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Analysis of β-Subunit-dependent GABAA Receptor Modulation and Behavioral Effects of Valerenic Acid Derivatives.

S Khom, J Hintersteiner, D Luger, M Haider, G Pototschnig, M D Mihovilovic, C Schwarzer, S Hering

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Intricacies of GABAInternational journal of molecular sciences · 2021
    Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

S KhomDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.) sophia.khom@univie.ac.at schwarzer.christoph@i-med.ac.at.
J HintersteinerDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
D LugerDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
M HaiderDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
G PototschnigDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
M D MihovilovicDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
C SchwarzerDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
S HeringDepartment of Pharmacology and Toxicology, University of Vienna, Vienna, Austria (S.K., J.H., D.L., S.H.); Institute of Applied Synthetic Chemistry, TU Wien, Vienna, Austria (M.H., G.P., M.D.M.); and Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria (C.S.).
Innsbruck Medical University · ATTU Wien · ATUniversität Innsbruck · ATUniversity of Vienna · AT

Funding

Austrian Science Fund FWF W 1232
6 · The paper itself

Abstract

Valerenic acid (VA)-a β2/3-selective GABA type A (GABAA) receptor modulator-displays anxiolytic and anticonvulsive effects in mice devoid of sedation, making VA an interesting drug candidate. Here we analyzed β-subunit-dependent enhancement of GABA-induced chloride currents (IGABA) by a library of VA derivatives and studied their effects on pentylenetetrazole (PTZ)-induced seizure threshold and locomotion. Compound-induced IGABA enhancement was determined in oocytes expressing α1β1γ2S, α1β2γ2S, or α1β3γ2S receptors. Effects on seizure threshold and locomotion were studied using C57BL/6N mice and compared with saline-treated controls. β2/3-selective VA derivatives such as VA-amide (VA-A) modulating α1β3γ2S (VA-A: Emax = 972 ± 69%, n = 6, P < 0.05) and α1β2γ2S receptors (Emax = 1119 ± 72%, n = 6, P < 0.05) more efficaciously than VA (α1β3γ2S: VA: Emax = 632 ± 88%, n = 9 versus α1β2γ2S: VA: Emax = 721 ± 68%, n = 6) displayed significantly more pronounced seizure threshold elevation than VA (saline control: 40.4 ± 1.4 mg/kg PTZ versus VA 10 mg/kg: 49.0 ± 1.8 mg/kg PTZ versus VA-A 3 mg/kg: 57.9 ± 1.9 mg/kg PTZ, P < 0.05). Similarly, VA's methylamide (VA-MA) enhancing IGABA through β3-containing receptors more efficaciously than VA (Emax = 1043 ± 57%, P < 0.01, n = 6) displayed stronger anticonvulsive effects. Increased potency of IGABA enhancement and anticonvulsive effects at lower doses compared with VA were observed for VA-tetrazole (α1β3γ2S: VA-TET: EC50 = 6.0 ± 1.0 μM, P < 0.05; VA-TET: 0.3 mg/kg: 47.3 ± 0.5 mg/kg PTZ versus VA: 10 mg/kg: 49.0 ± 1.8 mg/kg PTZ, P < 0.05). At higher doses (≥10 mg/kg), VA-A, VA-MA, and VA-TET reduced locomotion. In contrast, unselective VA derivatives induced anticonvulsive effects only at high doses (30 mg/kg) or did not display any behavioral effects. Our data indicate that the β2/3-selective compounds VA-A, VA-MA, and VA-TET induce anticonvulsive effects at low doses (≤10 mg/kg), whereas impairment of locomotion was observed at doses ≥10 mg/kg.

Indexed as

AnimalsBehavior, AnimalDose-Response Relationship, DrugFemaleIndenesMicePentylenetetrazoleReceptors, GABA-ASeizuresSesquiterpenesXenopus laevisIndenesPentylenetetrazoleReceptors, GABA-ASesquiterpenesvalerenic acid

Identifiers

PMID27190170
PMCPMC4885513
OpenAlexW2336614723

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.