Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22

Anwen M. Krause-Heuer, Rheaclare Fraser-Spears, Jeremy C. Dobrowolski, Mark E. Ashford, Naomi A. Wyatt, Maxine P. Roberts, Georgianna G. Gould, Wai Ching Cheah, Clarissa K.L. Ng, Mohan Bhadbhade, Bo Zhang, Ivan Greguric, Nial J. Wheate, Naresh Kumar, Wouter Koek, Paul D. Callaghan, Lynette C. Daws, Benjamin H. Fraser

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Herein we describe the synthesis and evaluation of antidepressant properties of seven analogues (1–7) of the low affinity/high capacity transporter blocker decynium-22 (D-22). All analogues (1–7) were synthesized via base promoted coupling reactions between N-alkylated-2-methylquinolinium iodides or N-alkylated-4-methylquinolinium iodides and electrophilic N-alkylated-2-iodoquinolinium iodides. All final compounds were purified by re-crystallization or preparative HPLC and initial evaluation studies included; 1) screening for in vitro α1-adrenoceptor activity (a property that can lead to unwanted side-effects), 2) measuring antidepressant-like activity in a mouse tail suspension test (TST), and 3) measuring effects upon mouse locomotion. The results showed some analogues have lower affinities at α1-adrenoceptors compared to D-22 and showed antidepressant-like activity without the need for co-administration of SSRIs. Additionally, many analogues did not affect mouse locomotion to the same extent as D-22. Plans for additional evaluations of these promising analogues, including measurement of antidepressant-like activity with co-administration of selective serotonin re-uptake inhibitors (SSRIs), are outlined.

Original languageEnglish (US)
Pages (from-to)476-487
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume137
DOIs
StatePublished - 2017

Keywords

  • Adrenoceptor
  • Antidepressant-like activity
  • Antidepressants
  • Decynium-22
  • Depression
  • SSRIs

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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