Anxiolytic-Like and Antidepressant Effects of a 13H-indolo[2,3-a]thiopyrano[2,3-g]quinolizine Derivative
Carlos E. Castillo-Espinoza,
María Leonor González-Rivera,
Alberto Medina-Ortiz,
Juan Carlos Barragan-Galvez,
Sergio Hidalgo-Figueroa,
David Cruz Cruz,
Martha Alicia Deveze-Alvarez,
Gerardo González-García,
Clarisa Villegas Gómez,
Angel Josabad Alonso-Castro
Affiliations
Carlos E. Castillo-Espinoza
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
María Leonor González-Rivera
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Alberto Medina-Ortiz
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Juan Carlos Barragan-Galvez
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Sergio Hidalgo-Figueroa
CONAHCyT-División de Biología Molecular/Instituto Potosino de Investigación Científica y Tecnológica A.C., San Luis Potosi, San Luis Potosi 78216, Mexico
David Cruz Cruz
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Martha Alicia Deveze-Alvarez
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Gerardo González-García
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Clarisa Villegas Gómez
Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Angel Josabad Alonso-Castro
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N Guanajuato, Guanajuato 36050, Mexico
Depressive and anxiety disorders constitute some of the most prevalent mental disorders around the world. For years, the development of new lead compounds for drug discovery in this field has been an area of great attention. Recently, a series of tetrahydrocarbazole derivatives have demonstrated important anxiolytic-like activity, associated with their structures and stereochemistry. Here, we present a study of the antidepressant effect and anxiolytic-like activity of a fused thiopyrano-piperidone-tetrahydrocarboline (compound 4). The antidepressant and anxiolytic-like effects of 4 (1–50 mg/kg p.o.) were assessed with the tail suspension test and the hole-board test, respectively. This study determined the possible mechanisms involved in the anxiolytic-like actions of 4 using inhibitors or neurotransmission and evaluated its interaction with 5HT2A receptors using a molecular docking study. As an analog to the tetrahydrocarbazole core, the tetrahydrocarboline derivative showed anxiolytic-like activity (ED50 = 13 mg/kg p.o.) in the hole-board test, with a comparable effect to the reference drug, 1.5 mg/kg clonazepam, with the possible participation of the serotonergic system.
