Anwen M Krause-Heuer1, Rheaclare Fraser-Spears2, Jeremy C Dobrowolski3, Mark E Ashford1, Naomi A Wyatt1, Maxine P Roberts1, Georgianna G Gould2, Wai-Ching Cheah1, Clarissa K L Ng1, Mohan Bhadbhade3, Bo Zhang4, Ivan Greguric1, Nial J Wheate5, Naresh Kumar3, Wouter Koek6, Paul D Callaghan1, Lynette C Daws7, Benjamin H Fraser8. 1. The Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Australia. 2. Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. 3. School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia. 4. The Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Australia; Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. 5. Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. 6. Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. 7. Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA; Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Electronic address: daws@uthscsa.edu. 8. The Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC NSW 2232, Australia. Electronic address: benjamin.fraser@ansto.gov.au.
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.
Herein we describe the synthesis ann class="Chemical">d 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.
Authors: Rebecca E Horton; Deana M Apple; W Anthony Owens; Nicole L Baganz; Sonia Cano; Nathan C Mitchell; Melissa Vitela; Georgianna G Gould; Wouter Koek; Lynette C Daws Journal: J Neurosci Date: 2013-06-19 Impact factor: 6.167
Authors: Nicole L Baganz; Rebecca E Horton; Alfredo S Calderon; W Anthony Owens; Jaclyn L Munn; Lora T Watts; Nina Koldzic-Zivanovic; Nathaniel A Jeske; Wouter Koek; Glenn M Toney; Lynette C Daws Journal: Proc Natl Acad Sci U S A Date: 2008-11-24 Impact factor: 11.205
Authors: Alejandro Orrico-Sanchez; Laetitia Chausset-Boissarie; Rodolphe Alves de Sousa; Basile Coutens; Sara Rezai Amin; Vincent Vialou; Franck Louis; Assia Hessani; Patrick M Dansette; Teodoro Zornoza; Carole Gruszczynski; Bruno Giros; Bruno P Guiard; Francine Acher; Nicolas Pietrancosta; Sophie Gautron Journal: Mol Psychiatry Date: 2019-10-16 Impact factor: 15.992
Authors: Rheaclare Fraser-Spears; Anwen M Krause-Heuer; Mohamed Basiouny; Felix P Mayer; Retrouvailles Manishimwe; Naomi A Wyatt; Jeremy C Dobrowolski; Maxine P Roberts; Ivan Greguric; Naresh Kumar; Wouter Koek; Harald H Sitte; Paul D Callaghan; Benjamin H Fraser; Lynette C Daws Journal: Eur J Pharmacol Date: 2018-10-25 Impact factor: 5.195
Authors: Georgianna G Gould; Priscilla A Barba-Escobedo; Rebecca E Horton; Lynette C Daws Journal: Front Pharmacol Date: 2022-06-09 Impact factor: 5.988