DFT-based QSAR and Action Mechanism of Phenylalkylamine and Tryptamine Hallucinogens

DFT/B3LYP/6-311G＋（d,p） basis set including solvent effect was first used to calculate a set of molecular descriptors of 55 phenylalkylamine and 20 tryptamine compounds with hallucinogenic activity. Four quantitative structure-activity relationship （QSAR） models of the hallucinogenic activity for phenylalkylamines and tryptamines were obtained by employing multiple linear regression （MLR） method. The QSAR analysis indicated that electron-related descriptors were major contributors to the hallucinogenic activities of phenylalkylamines and tryp- tamines. In addition, electron-unrelated descriptors have some impact on the hallucinogenic activities of phenylal- kylamines. Based on the results of QSAR study, a novel Conformation Complementary Judgement, Transformation and Induction （CCJTI） model had been proposed to explain different action mechanisms of phenylalkylamines and tryptamines with their target receptors. It was concluded that phenylalkylamines might combine with receptor by electronic effect, but steric factor could affect it also, whereas tryptamines could act only through the electronic effect.

Neuronal and peripheral damages induced by synthetic psychoactive substances: an update of recent findings from human and animal studies

Preclinical and clinical studies indicate that synthetic psychoactive substances,in addition to having abuse potential,may elicit toxic effects of varying severity at the peripheral and central levels.Nowadays,toxicity induced by synthetic psychoactive substances poses a serious harm for health,since recreational use of these substances is on the rise among young and adult people.The present review summarizes recent findings on the peripheral and central toxicity elicited by “old” and “new” synthetic psychoactive substances in humans and experimental animals,focusing on amphetamine derivatives,hallucinogen and dissociative drugs and synthetic cannabinoids.

How do serotonergic psychedelics treat depression:The potential role of neuroplasticity

Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants.One such novel antidepressant is ketamine,which has demonstrated both clinically promising results and contributed to new explanatory models of depression,including the potential role of neuroplasticity in depression.Early clinical trials are now showing promising results of serotonergic psychedelics for depression;however,their mechanism of action remains poorly understood.This paper seeks to review the effect of depression,classic antidepressants,ketamine,and serotonergic psychedelics on markers of neuroplasticity at a cellular,molecular,electrophysiological,functional,structural,and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.

Structure-activity Relationship Model for Predicting the Hallucinogenic Activity of Phenylalkylamines

A Quantitative Structure-activity Relationship（QSAR） model was developed to predict the hallucinogenic activity of phenylalkylamines by Artificial Neural Network（ANN） method.Each compound was represented by the calculated structural descriptors involving constitutional,topological,geometrical,electrostatic and quantum-chemical features of compound.The ANN method produced a nonlinear and seven-descriptor QSAR model with a standard error S = 0.0128 and a correlation coefficient R = 0.9752.The electronic properties of 75 phenylalkylamines were calculated with Gaussian 03 program at the DFT/B3LYP/6-311＋G（d,p） level.The quantum chemical analyses were performed from two aspects of frontier molecular orbital and charge distribution.The results show that seven structural describers are crucial to the hallucinogenic activity of phenylalkylamines and that the para-and ortho-positions could be active sites acting as electron donors.