Structures of novel psychoactive substances are based on the structure activity relationship (SAR) of existing drugs of abuse. The study identified links between structural modifications and toxicities, adverse and physiological effects of cannabinoids, cathinones and opioids. Literature review identified the structural backbone, toxicities, adverse and physiological effects of cannabinoids, cathinones and opioids. SAR of cannabinoids, cathinones and opioids was based on amino alkylindoles, cathinone derivatives and fentanyl derivatives. Synthetic cannabinoids XLR-11 and MDMB-CHMICA have been linked to acute kidney injury due to over stimulation of CB1 receptors. The synthetic cathinones MDPV and -PVP cause a higher occurrence of psychosis and delirium compared to other synthetic cathinones due to inhibitory uptake effects at dopamine and norepinephrine transporters. Fentanyl analogues having a lower lipophilic value than fentanyl had a shorter duration of physiological effects compared to fentanyl analogues having higher lipophilic values than fentanyl. The study contributes to an explanation of the higher potencies, toxicities and adverse effects associated with synthetic drugs.
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