Identification and pharmacological properties of 2-(1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (MDMB-INACA), N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (ADB-INACA), and N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-hexyl-1H-indazole-3-carboxamide (ADB-HINACA).

Abstract

Synthetic cannabinoids (SCs) are an evolving class of new psychoactive substances (NPS) with structurally various compounds that are increasing over the past few years. Therefore, they are initially hard to identify because of the lack of analytical information. Moreover, there is little to no information regarding the pharmacology of these compounds despite human abuse. In the present study, gas chromatography-mass spectrometry (GC-MS), ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS), and nuclear magnetic resonance (NMR) spectroscopy were used to identify the structure of three compounds obtained from seized materials. The pharmacological properties of these compounds were evaluated by subsequent behavioral testing, including von Frey and cold allodynia tests. The results indicated that these compounds were determined to be 2-(1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (MDMB-INACA), N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (ADB-INACA), and N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-hexyl-1H-indazole-3-carboxamide (ADB-HINACA) via GC-MS, UPLC-Q-TOF MS and NMR analysis, and they can attenuate mechanical and cold allodynia induced by paclitaxel in rats with peripheral neuropathy. Compared with MDMB-INACA and ADB-HINACA, ADB-INACA showed better analgesic effects on paclitaxel-induced peripheral neuropathy (PIPN) in rats, and its effect was similar to that of the positive drug N'-(1-hexyl-2-oxoindolin-3-ylidene) benzohydrazide (MDA-19).