# Characterization and Metabolism of Drug Products Containing the Cocaine-Like New Psychoactive Substances Indatraline and Troparil

## TL;DR

This study explores how two new psychoactive substances, indatraline and troparil, are metabolized in the body, focusing on their breakdown in rats and human liver samples.

## Contribution

The study provides a detailed characterization of the metabolism of indatraline and troparil, identifying specific phase I and II metabolites in rat urine and human liver incubations.

## Key findings

- Indatraline forms two phase I and four phase II metabolites, with aromatic hydroxylation and glucuronidation as key steps.
- Troparil forms four phase I and three phase II metabolites, with demethylation and hydroxylation as main metabolic processes.
- Indatraline metabolites were detectable in rat urine but not the parent compound, while troparil phase I metabolites were found in both rat urine and human liver incubations.

## Abstract

With a rising demand of cocaine over the last years, it is likely that unregulated new psychoactive substances with similar effects such as indatraline ((1R,3S)-3-(3,4-dichlorophenyl)-N-methyl-2,3-dihydro-1H-inden-1-amine) and troparil (Methyl (1R,2S,3S,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate) become popular as well. Both substances share a similar pharmacological profile as cocaine, while their potency is higher, and their duration of action is longer. This study investigated their metabolic fate in rat urine and incubations using pooled human liver S9 fraction (pHLS9). Indatraline formed two phase I and four phase II metabolites, with aromatic hydroxylation and glucuronidation being the main metabolic steps. All metabolites were detected in rat urine, while the parent compound was not detectable. Although low in abundance, indatraline metabolites were well identifiable due to their specific isotopic patterns caused by chlorine. Troparil formed four phase I and three phase II metabolites, with demethylation being the main metabolic step. Hydroxylation of the tropane ring, the phenyl ring, and combinations of these steps, as well as glucuronidation, were found. Phase I metabolites were detectable in rat urine and pHLS9, while phase II metabolites were only detectable in rat urine.