{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T20:57:38Z","timestamp":1768424258527,"version":"3.49.0"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Oligoarginine peptides, known mostly for their cell-penetrating properties, are also inhibitors of the nicotinic acetylcholine receptors (nAChRs). Since octa-arginine (R8) inhibits \u03b19\u03b110 nAChR and suppresses neuropathic pain, we checked if other polycationic compounds containing amino and\/or guanidino groups could be effective and tested the activity of the disulfide-fixed \u201ccyclo\u201dR8, a series of biogenic polyamines (putrescine, spermidine, and spermine), <jats:italic>C<\/jats:italic>-methylated spermine analogs, agmatine and its analogs, as well as acylpolyamine argiotoxin-636 from spider venom. Their inhibitory potency on muscle-type, \u03b17 and \u03b19\u03b110 nAChRs was determined using radioligand analysis, electrophysiology, and calcium imaging. \u201cCyclo\u201dR8 showed similar activity to that of R8 against \u03b19\u03b110 nAChR (IC<jats:sub>50<\/jats:sub> \u2248 60\u00a0nM). Biogenic polyamines as well as agmatine and its analogs displayed low activity on muscle-type <jats:italic>Torpedo californica<\/jats:italic>, as well as \u03b17 and \u03b19\u03b110 nAChRs, which increased with chain length, the most active being spermine and its <jats:italic>C<\/jats:italic>-methylated derivatives having IC<jats:sub>50<\/jats:sub> of about 30\u00a0\u03bcM against muscle-type <jats:italic>T. californica<\/jats:italic> nAChR. Argiotoxin-636, which contains a polyamine backbone and terminal guanidino group, also weakly inhibited <jats:italic>T. californica<\/jats:italic> nAChR (IC<jats:sub>50<\/jats:sub> \u2248 15\u00a0\u03bcM), but it revealed high potency against rat \u03b19\u03b110 nAChR (IC<jats:sub>50<\/jats:sub> \u2248 200\u00a0nM). We conclude that oligoarginines and similar polycationic compounds effectively inhibiting \u03b19\u03b110 nAChR may serve as a basis for the development of analgesics to reduce neuropathic pain.<\/jats:p>","DOI":"10.3389\/fphar.2023.1327603","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T11:05:48Z","timestamp":1702638348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of nicotinic acetylcholine receptors by oligoarginine peptides and polyamine-related compounds"],"prefix":"10.3389","volume":"14","author":[{"given":"Lucy O.","family":"Ojomoko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V.","family":"Kryukova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya S.","family":"Egorova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur I.","family":"Salikhov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyubov A.","family":"Epifanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria A.","family":"Denisova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex R.","family":"Khomutov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry A.","family":"Sukhov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Vassilevski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim A.","family":"Khomutov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor I.","family":"Tsetlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina V.","family":"Shelukhina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/0304-3940(87)90237-0","article-title":"Argiopin blocks the glutamate responses and sensorimotor transmission in motoneurones of isolated frog spinal cord","volume":"83","author":"Antonov","year":"1987","journal-title":"Neurosci. 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