Psychoactive Drugs—From Chemical Structure to Oxidative Stress Related to Dopaminergic Neurotransmission. A Review

Abstract

Nowadays, more and more young people want to experience illegal, psychoactive substances, without knowing the risks of exposure. Besides affecting social life, psychoactive substances also have an important effect on consumer health. We summarized and analyzed the published literature data with reference to the mechanism of free radical generation and the link between chemical structure and oxidative stress related to dopaminergic neurotransmission. This review presents data on the physicochemical properties, on the ability to cross the blood brain barrier, the chemical structure activity relationship (SAR), and possible mechanisms by which neuronal injuries occur due to oxidative stress as a result of drug abuse such as “bath salts”, amphetamines, or cocaine. The mechanisms of action of ingested compounds or their metabolites involve intermediate steps in which free radicals are generated. The brain is strongly affected by the consumption of such substances, facilitating the induction of neurodegenerative diseases. It can be concluded that neurotoxicity is associated with drug abuse. Dependence and oxidative stress are linked to inhibition of neurogenesis and the onset of neuronal death. Understanding the pathological mechanisms following oxidative attack can be a starting point in the development of new therapeutic targets.

Functional Genomic Analysis of Amphetamine Sensitivity in Drosophila

“…upregulated genes had a higher number of specific differentially enriched functional annotation terms (as opposed to general ones) than downregulated genes, which did not show any particular predominant categories in the enrichment analysis (Figure 2A, Supplementary Figure 1E). Major functional categories that were predominantly enriched in the DATindependent group, and therefore represented a common response to the drug between WT and DAT mutant, included oxidation-reduction process and glutathione metabolism (Figure 2, red), consistent with the presence of a general xenobiotic response to drug exposure (37).…”

A Scientometric Visualization Analysis for Molecular Mechanisms of Substance Abuse and Its Neurotoxicity From 1997 to 2021

“…The neurotoxic effects of abused substances could be described as inhibiting (e.g., opioids, cannabinoids, nicotine) or stimulating (e.g., cocaine and amphetamines) neurotransmitters, decreasing dopamine and serotonin reserves by inactivating their transporters, reducing vesicular monoamine transporters, and activating alpha-(2)-adrenergic receptors (Volkow et al, 2001;Cozzi and Foley, 2003;Garrido et al, 2005;Jîtcã et al, 2021). Besides, studies also proved that tachykinins, especially substance P (SP), are linked to the terminal degeneration of dopamine through NK-1 receptor activity in substantia nigra for chronic methamphetamine abusers (Yu et al, 2002).…”

Current and novel pharmacological therapeutic approaches in Post-Traumatic Stress Disorder. A brief review

“…More frequent side effects have been reported in case of MDMA use than in case of CBD: dry mouth, nausea, anxiety, inability to urinate, bruxism, restlessness, sleep disturbances, depression [59] increase in heart rate, blood pressure and in body-temperature and at higher doses, potentially fatal serotonin syndrome. The latter side effects can be attributed to the increased serotonin levels, which can be indirectly correlated with oxidative stress via 5-HT 2A receptors activation which leads to accumulation of DA in Nac [58,61].…”