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 language | English (US) |
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Pages (from-to) | 476-487 |
Number of pages | 12 |
Journal | European Journal of Medicinal Chemistry |
Volume | 137 |
DOIs | |
State | Published - 2017 |
Keywords
- Adrenoceptor
- Antidepressant-like activity
- Antidepressants
- Decynium-22
- Depression
- SSRIs
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry