EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

N-propyl-2,2-diphenyl-2-hydroxyacetamide, a novel α-hydroxyamide with anticonvulsant, anxiolytic and antidepressant-like effects that inhibits voltage-gated sodium channels



N-propyl-2,2-diphenyl-2-hydroxyacetamide, a novel α-hydroxyamide with anticonvulsant, anxiolytic and antidepressant-like effects that inhibits voltage-gated sodium channels



European Journal of Pharmacology: -



In patients with epilepsy, anxiety and depression are the most frequent psychiatric comorbidities but they often remain unrecognized and untreated. We report herein the antidepressant-like activity in two animal models, tail suspension and forced swimming tests, of six anticonvulsants α-hydroxyamides. From these, N-propyl-2,2-diphenyl-2-hydroxyacetamide (compound 5) emerged not only as the most active as anticonvulsant (ED50= 2.5mg/kg, MES test), but it showed the most remarkable antidepressant-like effect in the tail suspension and forced swimming tests (0.3-30mg/kg, i.p.); and, also, anxiolytic-like action in the plus maze test (3-10mg/kg, i.p.) in mice. Studies of its mechanism of action, by means of its capacity to act via the GABAA receptor ([3H]-flunitrazepam binding assay); the 5-HT1A receptor ([3H]-8-OH-DPAT binding assay) and the voltage-gated sodium channels (either using the patch clamp technique in hNav 1.2 expressed in HEK293 cell line or using veratrine, in vivo) were attempted. The results demonstrated that its effects are not likely related to 5-HT1A or GABAAergic receptors and that its anticonvulsant and antidepressant-like effect could be due to its voltage-gated sodium channel blocking properties.

(PDF emailed within 0-6 h: $19.90)

Accession: 065362555

Download citation: RISBibTeXText

PMID: 29217174

DOI: 10.1016/j.ejphar.2017.11.048



Related references

The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: A comparison with carbamazepine and oxcarbazepine. Neurochemistry International 40(5): 435-440, April, 2002

Effects of decabrominated diphenyl ether (PBDE 209) on voltage-gated sodium channels in primary cultured rat hippocampal neurons. Environmental Toxicology 25(4): 400-408, 2011

Interaction of the novel anticonvulsant, BIA 2-093, with voltage-gated sodium channels: Comparison with carbamazepine. Epilepsia 42(5): 600-608, 2001

Characterization of the anticonvulsant properties of Co 102862, a novel blocker of voltage-gated sodium channels. Society for Neuroscience Abstracts 23(1-2): 2163, 1997

Characterization of the anticonvulsant and pharmacokinetic properties of Co 102862, a novel blocker of voltage-gated sodium channels. Epilepsia 38(SUPPL 8): 15, 1997

The anticonvulsant SGB-017 (ADCI) blocks voltage-gated sodium channels in rat and human neurons: comparison with carbamazepine. Epilepsia 41(3): 263-270, 2000

The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Molecular Pharmacology 73(1): 157-169, 2007

Tri-cyclic antidepressant agents and their metabolites block voltage-gated SCN3A sodium channels. Biophysical Journal 84(2 Part 2): 214a, February, 2003

Merging Structural Motifs of Functionalized Amino Acids and α-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-gated Sodium Channels and in the Treatment of Neuropathic Pain. Acs Chemical Neuroscience 2(6): 317-322, 2011

Risperidone inhibits voltage-gated sodium channels. European Journal of Pharmacology 728: 100-106, 2015

Cloning of a novel voltage gated sodium channel from human cardiac and skeletal muscle evidence for a new gene sub family of voltage gated sodium channels. Biophysical Journal 61(2 PART 2): A108, 1992

The anticonvulsant SGB-017, an NMDA receptor antagonist, blocks voltage-gated sodium channels in rat and human neurons Comparison with carbamazepine. Society for Neuroscience Abstracts 24(1-2): 1939, 1998

Vitex negundo induces an anticonvulsant effect by inhibiting voltage gated sodium channels in murine Neuro 2A cell line. Pakistan Journal of Pharmaceutical Sciences 31(1(Suppl.)): 297-303, 2018

A spider toxin that inhibits activation of voltage-gated sodium channels. Biophysical Journal 82(1 Part 2): 85a, January, 2002

The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by associating with domain-3. Febs Letters 580(5): 1360-1364, 2006