Evaluation of the pharmacological descriptors related to the induction of antidepressant activity and its prediction by QSAR/QRAR methods.
ABSTRACT Antidepressants are psychiatric agents used for the treatment of different types of depression, being at present amongst the most commonly prescribed drugs, while their effectiveness and adverse effects are still the subject of many studies. To reduce the inefficiency of known antidepressants caused by their side-effects, many research efforts have recently focused on the development of improved strategies for new antidepressants drug design. For this reason it is necessary to apply very fast and precise techniques, such as QSAR (Quantitative Structure-Activity Relationships) and QRAR (Quantitative Retention-Activity Relationship), which are capable to analyze and predict the biological activity for these structures, taking in account the possible changes of the molecular structures and chromatographic parameters. We discuss the pharmaceutical descriptors (van der Waals, electrostatic, hydrophobicity, hydrogen donor/acceptor bond, Verloop's parameters, polar area) involved in QSAR and also chromatographic parameters involved in QRAR studies of antidepressants. Antidepressant activities of alkanol piperazine, acetamides, arylpiperazines, thienopyrimidinone derivatives (as preclinical antidepressants) and also the antidepressants already used in clinical practice are mentioned.
SourceAvailable from: Nikola Stevanovic[Show abstract] [Hide abstract]
ABSTRACT: The objectives of this study were to gain insights into the structure-retention and structure-lipophilicity relationships of series of twenty antidepressants and to propose model for estimating their retention and lipophilicity. The lipophilicity of antidepressants has been determined by reversed-phase thin-layer chromatography using binary methanol– water mobile phases. The chemical structures of the antidepressants have been characterized by molecular descriptors which are calculated from the structure and related to the chromatographic retention parameters as well as chromatographically determinated lipophilicity parameters by multiple linear regression analysis. The obtained models were used for interpretation of the lipophilicity and retention behavior of the investigated compounds.Letters in Drug Design & Discovery 02/2014; 11(2):162-168(7). DOI:10.2174/15701808113109990040 · 0.96 Impact Factor
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ABSTRACT: In this study, we synthesized eight novel 1-phenyl-2-(4-substituted-piperazin-1-yl)-propanol derivatives and evaluated their antidepressant-like activities. The chemical structures of the synthesised compounds were elucidated by spectroscopy and elemental analyses. Potential antidepressant-like effects of the test compounds (20 mg kg(-1)) were investigated using the tail-suspension test and modified forced swimming test (MFST) in mice. Additionally, the spontaneous locomotor activity of the mice was assessed using the activity cage apparatus. Both the reference drug fluoxetine (20 mg kg(-1)) and the test compounds 3a-3e and 3g significantly shortened the immobility time of the mice in both the behavioural tests. These test compounds also increased the swimming time in MFST without any change in the climbing duration. Compounds 3c-3e and 3g were significantly more potent in inducing these effects than 3a and 3b. None of the compounds changed the locomotor activities of the animals, thus antidepressant-like effects of test compounds were specific. The findings support those of previous studies that reported antidepressant-like activities of aryl alkanol piperazine derivatives.Archives of Pharmacal Research 04/2013; 36(7). DOI:10.1007/s12272-013-0119-1 · 1.75 Impact Factor