ArticleBiochemical pharmacology2013
GABAA receptor modulation by piperine and a non-TRPV1 activating derivative.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- A Systematic Review of the Anti-seizure and Antiepileptic Effects and Mechanisms of Piperine.Central nervous system agents in medicinal chemistry · 2025Pooled it
- A Pharmacological Perspective on Plant-derived Bioactive Molecules for Epilepsy.Neurochemical research · 2021Pooled it
- Subunit-specific inhibition of BK channels by piperine.Biophysical journal · 2024Article
- Effect of Black Pepper (Nutrients · 2022Article
- Piperine and Its Metabolite's Pharmacology in Neurodegenerative and Neurological Diseases.Biomedicines · 2022Review
- Remedia Sternutatoria over the Centuries: TRP Mediation.Molecules (Basel, Switzerland) · 2021Review
- Rational approaches for the design of various GABA modulators and their clinical progression.Molecular diversity · 2021Review
- Effects of gamma-aminobutyric acid and piperine on gene regulation in pig kidney epithelial cell lines.Asian-Australasian journal of animal sciences · 2020Article
- Article
- The role of Piper chaba Hunt. and its pure compound, piperine, on TRPV1 activation and adjuvant effect.BMC complementary medicine and therapies · 2020Article
- HPLC-based activity profiling for pharmacologically and toxicologically relevant natural products - principles and recent examples.Pharmaceutical biology · 2019Review
- A distinct structural mechanism underlies TRPV1 activation by piperine.Biochemical and biophysical research communications · 2019Article
- Black pepper and its bioactive constituent piperine: promising therapeutic strategies for oral lichen planus.Inflammopharmacology · 2019Review
- Anxiolytic and antidepressant profile of the methanolic extract of Piper nigrum fruits in beta-amyloid (1-42) rat model of Alzheimer's disease.Behavioral and brain functions : BBF · 2015Article
- Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.Frontiers in cellular neuroscience · 2015Article
- Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.Journal of medicinal chemistry · 2014Article
- Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood-brain barrier model for drug permeability studies.Fluids and barriers of the CNS · 2013Article
- Efficacy ofAyuArticle
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The action of piperine (the pungent component of pepper) and its derivative SCT-66 ((2E,4E)-5-(1,3-benzodioxol-5-yl))-N,N-diisobutyl-2,4-pentadienamide) on different gamma-aminobutyric acid (GABA) type A (GABA(A)) receptors, transient-receptor-potential-vanilloid-1 (TRPV1) receptors and behavioural effects were investigated. GABA(A) receptor subtypes and TRPV1 receptors were expressed in Xenopus laevis oocytes. Modulation of GABA-induced chloride currents (I(GABA)) by piperine and SCT-66 and activation of TRPV1 was studied using the two-microelectrode-voltage-clamp technique and fast perfusion. Their effects on explorative behaviour, thermoregulation and seizure threshold were analysed in mice. Piperine acted with similar potency on all GABA(A) receptor subtypes (EC₅₀ range: 42.8±7.6 μM (α₂β₂)-59.6±12.3 μM (α₃β₂). I(GABA) modulation by piperine did not require the presence of a γ(2S)-subunit, suggesting a binding site involving only α and β subunits. I(GABA) activation was slightly more efficacious on receptors formed from β(2/3) subunits (maximal I(GABA) stimulation through α₁β₃ receptors: 332±64% and α₁β₂: 271±36% vs. α₁β₁: 171±22%, p<0.05) and α₃-subunits (α₃β₂: 375±51% vs. α₅β₂:136±22%, p<0.05). Replacing the piperidine ring by a N,N-diisobutyl residue (SCT-66) prevents interactions with TRPV1 and simultaneously increases the potency and efficiency of GABA(A) receptor modulation. SCT-66 displayed greater efficacy on GABA(A) receptors than piperine, with different subunit-dependence. Both compounds induced anxiolytic, anticonvulsant effects and reduced locomotor activity; however, SCT-66 induced stronger anxiolysis without decreasing body temperature and without the proconvulsive effects of TRPV1 activation and thus may serve as a scaffold for the development of novel GABA(A) receptor modulators.
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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.