N‐Salicyloyltryptamine, a new anticonvulsant drug, acts on voltage‐dependent Na+, Ca2+, and K+ ion channels

• Published in: British journal of pharmacology Vol. 140; no. 7; pp. 1331 - 1339
• Main Authors: Araújo, Demétrius Antonio Machado, Mafra, Roberta Amaral, Rodrigues, Andréia Laura Prates, Miguel‐Silva, Válter, Beirão, Paulo Sérgio Lacerda, De Almeida, Reinaldo Nóbrega, Quintans, Lucindo, Souza, Maria Fátima Vanderlei de, Cruz, Jader Santos
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2003; Nature Publishing
• Subjects: Animals; Anticonvulsant; Anticonvulsants - pharmacology; Biological and medical sciences; calcium channels; Calcium Channels, L-Type - drug effects; Cell Line, Tumor; Dose-Response Relationship, Drug; Maxi‐BKCa; Medical sciences; N‐salicyloyltryptamine; patch clamp; Patch-Clamp Techniques; Pharmacology. Drug treatments; Pituitary Neoplasms - pathology; Potassium Channels - drug effects; Rats; Salicylates - pharmacology; sodium channels; Sodium Channels - drug effects; Tryptamines - pharmacology; Drug; patch clamp; Calcium; calcium channels; Electrophysiology; Patch clamp method; Anticonvulsant; Ionic channel; Inorganic element; Sodium; sodium channels; Maxi-BKCa; N-salicyloyltryptamine; Potassium
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705471

The aim of this work was to study the effects of N‐salicyloyltryptamine (STP), a novel anticonvulsant agent, on voltage‐gated ion channels in GH3 cells.
In this study, we show that STP at 17 μM inhibited up to 59.2±10.4% of the Ito and 73.1±8.56% of the IKD K+ currents in GH3 cells. Moreover, the inhibitory activity of the drug STP on K+ currents was dose‐dependent (IC50=34.6±8.14 μM for Ito) and partially reversible after washing off.
Repeated stimulation at 1 Hz (STP at 17 μM) led to the total disappearance of Ito current, and an enhancement of IKD.
In the cell‐attached configuration, application of STP to the bath increased the open probability of large‐conductance Ca2+‐activated K+ channels.
STP at 17 μM inhibited the L‐type Ca2+ current by 54.9±7.50% without any significant changes in the voltage dependence.
STP at 170 μM inhibited the TTX‐sensitive Na+ current by 22.1±2.41%. At a lower concentration (17 μM), no effect on INa was observed.
The pharmacological profile described here might contribute to the neuroprotective effect exerted by this compound in experimental ‘in vivo’ models.
British Journal of Pharmacology (2003) 140, 1331–1339. doi:10.1038/sj.bjp.0705471