1316288-58-0Relevant academic research and scientific papers
NO-SSRIs: Nitric oxide chimera drugs incorporating a selective serotonin reuptake inhibitor
Abdul-Hay, Samer,Schiefer, Isaac T.,Chandrasena, R. Esala P.,Li, Min,Abdelhamid, Ramy,Wang, Yue-Ting,Tavassoli, Ehsan,Michalsen, Bradley,Asghodom, Rezene T.,Luo, Jia,Thatcher, Gregory R. J.
supporting information; experimental part, p. 656 - 661 (2011/11/07)
Hybrid nitrate drugs have been reported to provide NO bioactivity to ameliorate side effects or to provide ancillary therapeutic activity. Hybrid nitrate selective serotonin reuptake inhibitors (NO-SSRIs) were prepared to improve the therapeutic profile of this drug class. A synthetic strategy for use of a thiocarbamate linker was developed, which in the case of NO-fluoxetine facilitated hydrolysis to fluoxetine at pH 7.4 within 7 h. In cell culture, NO-SSRIs were weak inhibitors of the serotonin transporter; however, in the forced swimming task (FST) in rats, NO-fluoxetine demonstrated classical antidepressant activity. Comparison of NO-fluoxetine, with fluoxetine, and an NO-chimera nitrate developed for Alzheimer's disease (GT-1061) were made in the step through passive avoidance (STPA) test of learning and memory in rats treated with scopolamine as an amnesic agent. Fluoxetine was inactive, whereas NO-fluoxetine and GT-1061 both restored long-term memory. GT-1061 also produced antidepressant behavior in FST. These data support the potential for NO-SSRIs to overcome the lag in onset of therapeutic action and provide cotherapy of neuropathologies concomitant with depression.
