In vitro toxicokinetics of cyclopropyl amphetamines (CPAs)

• Grant number: 25/00898-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: August 01, 2025
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: José Luiz da Costa
• Grantee: Leonardo Costalonga Rodrigues
• Supervisor: Lea Wagmann
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Saarland University, Homburg, Germany
• Associated to the scholarship: 22/00037-0 - Biotransformation studies and behavioral assays of new psychoactive substances through in vivo models using Zebrafish (Danio rerio), BP.DD

Abstract

The new psychoactive substances (NPS) are a large group of substances that can pose a public health threat. Given the pharmacology of most NPS has not yet been deeply investigated, notable additional problems can occur after their consumption. A better understanding of pharmacological or the toxic effects of these substances can provide valuable information, including the management of an intoxication case. Therefore, there is a continuous research need of understanding the toxicokinetics and toxicodynamics of NPS. Dimethoxyamphetamines were used as psychedelics for many years, considering its hallucinogenic properties and novel derivatives are expected to enter the drugs of abuse market in the future, such as cyclopropyl amphetamines (CPAs), characterized by the presence of a cyclopropyl ring in their chemical structure. Currently, there is a paucity of detailed information on CPAs in the scientific literature and public sources. The investigation of the toxicokinetics of CPA series can contribute with valuable information and in vitro experiments are well suitable for this. Considering that, the aim of this proposal is to investigate the toxicokinetics of eight of such novel compounds of CPA series by different evaluations including in vitro identification of metabolites in pooled human liver S9 fraction (pHLS9) incubations by liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS); in vitro metabolic stability; isozyme mapping; and determination of plasma protein binding.