In Vivo Pharmaco-Toxicological Characterization of Brorphine and its Possible Emerging Analogues Orphine, Fluorphine, Chlorphine and Iodorphine

Brorphine is a dangerous novel synthetic opioid (NSO) that has recently emerged on the illicit drug market of New Psychoactive Substances (NPS) and has been involved in multiple cases of intoxication and death worldwide. Although brorphine has recently been prohibited, its (halogenated) analogues orphine, chlorphine, fluorphine and iodorphine may be available on the NPS market, potentially posing new risks to public health. Therefore, the aim of this study is to characterize the acute effects of brorphine and its analogues in vivo. We investigated the acute effects after systemic administration of brorphine and 4 analogues (0.01–15 mg/kg i.p.) on mechanical and thermal analgesia, motor impairment, grip strength and cardiorespiratory changes in male CD-1 mice. Opioid receptor specificity was also investigated using naloxone (6 mg/kg i.p.) pre-treatment. All compounds increased mechanical and thermal analgesia, and impaired motor and cardiorespiratory parameters. Brorphine was the most potent of all tested compounds. The pre-treatment with naloxone prevented partially the analgesic, motor and cardio-respiratory impairments induced by brorphine and its analogues. These findings confirm the dangerous profile of brorphine and increase the alert on the possible emergence of new brorphine analogues and their possible association with a new wave of intoxication and death worldwide.