Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist

Research output: Contribution to journalJournal articleResearchpeer-review

Kristian Strømgaard, Ian R Mellor, Kim Andersen, Ioana Neagoe, Florentina Pluteanu, Peter N R Usherwood, Povl Krogsgaard-Larsen, Jerzy W Jaroszewski

Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro electrophysiological studies of nAChR demonstrated that decreasing the number of methylene groups from 12 to 11 significantly increased potency. Antagonism by PhTX-11, like that of PhTX-12, was only weakly voltage-dependent. When the methylene spacer was reduced further, antagonism was decreased below that of PhTX-12, and in some cases potentiation of ACh responses by up to 60% was observed.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry Letters
Volume12
Issue number8
Pages (from-to)1159-1162
Number of pages4
ISSN0960-894X
Publication statusPublished - 22 Apr 2002

    Research areas

  • Chromatography, High Pressure Liquid, Drug Evaluation, Preclinical, Mass Spectrometry, Nicotinic Antagonists, Patch-Clamp Techniques, Polyamines, Tyrosine

ID: 45823749