Pharmaco-toxicological effects of the novel third-generation fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice. In vitro and in vivo studies
| Autor: | Paolo Pinton, Fabrizio Vincenzi, Matteo Marti, Federica Nigro, Isabella Canazza, Alessandro Rimessi, Pier Andrea Borea, Adolfo Gregori, Fabiana Di Rosa, Andrea Ossato, Katia Varani |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Indazoles Indoles Cannabinoid receptor Socio-culturale Adamantane CHO Cells Catalepsy Pharmacology Designer Drugs Mice 03 medical and health sciences Cricetulus 0302 clinical medicine In vivo Cricetinae Synthetic cannabinoids Cannabinoid receptor type 2 Human CB1 receptor Neurotoxicity Δ9-THC Animals Humans Medicine Inverse agonist Pharmacology (medical) STS-135 Cells Cultured Mice Inbred ICR AB-FUBINACA Cannabinoids business.industry 5F-ADBINACA Biological activity Fluorine medicine.disease Psychiatry and Mental health 030104 developmental biology Neurology Neurology (clinical) business Locomotion 030217 neurology & neurosurgery medicine.drug |
| Popis: | Introduction 5F-ADBINACA, AB-FUBINACA, and STS-135 are 3 novel third-generation fluorinate synthetic cannabinoids that are illegally marketed as incense, herbal preparations, or research chemicals for their psychoactive cannabis-like effects. Methods The present study aims at investigating the in vitro and in vivo pharmacological activity of 5F-ADBINACA, AB-FUBINACA, and STS-135 in male CD-1 mice, comparing their in vivo effects with those caused by the administration of Δ9-THC and JWH-018. In vitro competition binding experiments revealed a nanomolar affinity and potency of the 5F-ADBINACA, AB-FUBINACA, and STS-135 on mouse and human CB1 and CB2 receptors. Moreover, these synthetic cannabinoids induced neurotoxicity in murine neuro-2a cells. Results In vivo studies showed that 5F-ADBINACA, AB-FUBINACA, and STS-135 induced hypothermia; increased pain threshold to both noxious mechanical and thermal stimuli; caused catalepsy; reduced motor activity; impaired sensorimotor responses (visual, acoustic, and tactile); caused seizures, myoclonia, and hyperreflexia; and promoted aggressiveness in mice. Behavioral and neurological effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251. Differently, the visual sensory response induced by STS-135 was only partly prevented by the AM 251, suggesting a CB1-independent mechanism. Conclusions For the first time, the present study demonstrates the pharmaco-toxicological effects induced by the administration of 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice and suggests their possible detrimental effects on human health. |
| Databáze: | OpenAIRE |
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