Anxiolytic activity of pyridoindole derivatives SMe1EC2 and SMe1M2: behavioral analysis using rat model

Abstract

Anxiety and mood disorders have become very significant affections in the last decades. According to WHO at least one mental disease occurred per year in 27% of EU inhabitants (more than 82 mil. people). It is estimated that by 2020, depression will be the main cause of morbidity in the developed countries. These circumstances call for research for new prospective drugs with anxiolytic and antidepressive properties exhibiting no toxicity and withdrawal effect and possessing beneficial properties, like antioxidant and/or neuroprotective effects. The aim of this study was to obtain information about psychopharmacological properties of pyridoindole derivatives SMe1EC2 and SMe1M2, using non-invasive behavioral methods in rats.The battery of ethological tests (open field, elevated plus-maze, light/dark box exploration, forced swim test) was used to obtain information about anxiolytic and antidepressant activity of the pyridoindole derivatives. The substances were administered intraperitoneally 30 minutes before the tests at doses of 1, 10 and 25 mg/kg.In the behavioral tests, SMe1EC2 was found to exert anxiolytic activity in elevated plus maze with no affection of locomotor activity. The highest dose of SMe1M2 increased the time spent in the lit part of the Light/Dark box, however this result was influenced by inhibition of motor activity of the rats. Similar findings were observed also in elevated plus-maze, although these results were not statistically significant.In conclusion, from the results of our study it is evident that both pyridoindoles acted on the CNS. In the highest dose, SMe1M2 was found to possess rather sedative than anxiolytic or antidepressant activity.

Interaction of Cocaine- and Amphetamine-regulated Transcript and Neuropeptide Y on Behavior in the Central Nervous System

“…The increases in ambulation and rearing in the open field test in the NPY group and the time spent on and number of entries into the open arms in the elevated plus maze test demonstrated that NPY has anxiolytic properties, which is consistent with previous studies (38,39,40). The results of studies on the paraventricular nucleus, basolateral amygdala (BLA), and central amygdala demonstrated that NPY exerts its anxiolytic effect mostly via the Y1 receptor and also that the ICV administration of NPY or Y1 receptor agonists cause anxiolytic effects in experimental anxiety models (41,42,43).…”

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

“…For the electrophysiological experiments, SMe1EC2M3 was administered intravenously (i.v., via a catheter placed in the lateral tail vein) at the doses 0.5–2.5 mg/kg. The doses were chosen according to our previous studies with pyridoindole derivatives [42,43]. Chloral hydrate, WAY100135, and yohimbine were purchased from Lambda Life, a.s. (Bratislava, Slovakia) and dissolved in vehicle.…”

Key Targets for Multi-Target Ligands Designed to Combat Neurodegeneration

“…Four ethological tests with rats (open field, elevated plus-maze, light/dark box exploration, forced swim test) were used to obtain information about anxiolytic and antidepressant activity of SMe1EC2 (Sedláčková et al, 2011 ). The substance was administered intraperitoneally 30 min before the tests at doses of 1, 10, and 25 mg/kg.…”