Evaluation of the Pharmacological Descriptors Related to the Induction of Antidepressant Activity and its Prediction by QSAR/QRAR Methods
Dept. of Anatomy, Animal Physiology and Biophysics, University of Bucharest, Faculty of Biology, 91-95 Spl. Independentei, Bucharest-076201, Romania. Mini Reviews in Medicinal Chemistry
(Impact Factor: 2.9).
06/2012; 12(6):467-76. DOI: 10.2174/138955712800493834
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.
Available from: Nikola Stevanovic
- "Antidepressants are psychiatric agents used for the treatment of different types of depression  . It is very important to control the antidepressants distribution to the place of action. "
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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.
Available from: Yusuf Ozturk
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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.
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ABSTRACT: The central nervous system is endowed with complex mechanisms of defense. However, these protection mechanisms fail in the presence of risk factors such as genetic mutations, environmental factors (bisphenol A, polycyclic aromatic hydrocarbons (PAHs), polyfluoroalkyl chemicals) or social stress and psychiatric disorders (anxiety, depression, psychosis, attention deficits) appear. Critical psychiatric conditions treatment consists in administration of antidepressants and antipsychotics drugs. These drugs are widely prescribed, but their efficiency in controlling mental symptoms is an important point in current clinical studies. Antidepressants and antipsychotics register several side effects and their interactions with other polycyclic aromatic hydrocarbons are well established. Research is focused upon reducing these side effects and understanding their pharmacodynamic and pharmacokinetic properties in order to develop advanced methods to predict induced pharmacological events. Here we intend to detail recent advances in the field of structure-activity relationship (QSAR) applied to antidepressants and antipsychotics with polycyclic aromatic structure as last generation drugs used in central nervous system disorders. We present the biological activity of large series of psychiatric drugs predicted by 2D and 3D-QSAR dependent and independent molecules alignment. Predicted biological activities were correlated with common pharmaceutical descriptors as steric, electronic hydrogen donor/acceptor bond but also new components of QSAR models as membrane ions' contributions to the antagonism of these drugs at membrane receptors are presented. The paper refers both to preclinical tested molecules and to already known antidepressants and antipsychotics based on a large variety of polycyclic aromatic structure. Drug potency decrease in the presence of PAHs is also discussed.
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