Abstract
A greater percentage of depressed patients respond to combined treatment with a tricyclic antidepressant and the tetracyclic antidepressant mianserin than to treatment with these drugs given alone. The functional sensitivity of the 5-hydroxytryptamine (5-HT) 1A receptor, and the functional interaction between the 5-HT 1A and the 5-HT 2 receptors were investigated after treatment with despiramine and mianserin either alone or combined for 21–28 days. Pretreatment with desipramine and mianserin in combination induced the most intense 5-HT syndrome and the greatest fall in colonic temperature after injection of the 5-HT 1A agonist 8-hydroxy-2-(di- n-propylamino)-tetralin (8-OH-DPAT). The rats pretreated with desipramine alone had the largest elevation of the response temperature in the increasing temperature hot-plate test after injection of 8-OH-DPAT. After the combined pretreatment with desipramine and mianserin, no enhanced functional response in these tests was found when the 5-HT 1A and the 5-HT 2 receptors were stimulated simultaneously using 8-OH-DPAT and the 5-HT 2 agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropine HCl (DOI), contrasting the findings for desipramine or mianserin treatments given alone, where an increased functional response was found for the colonic temperature and the response temperature in the increasing temperature hot-plate test. In vitro receptor binding using [ 3H]-8-OH-DPAT as ligand revealed an increase in K d and K max in the spinal cord after chronic treatment with the combination of desipramine and mianserin. In the hippocampus and the frontal cortex the changes were small. Thus, the combination of desipramine and mianserin increased the functional response to 5-HT 1A receptor stimulation, and decreased the response to simultaneous stimulation of the 5-HT 1A and 5-HT 2 receptors, when compared to treatments with either one of the antidepressants alone, or controls. These rather large functional changes were not clearly reflected in the receptor binding study, indicating that changes in the postreceptor signal transduction may be of importance.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
