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Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies

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Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies

Content Provider	Springer Nature Link
Author	Canazza, Isabella Ossato, Andrea Trapella, Claudio Fantinati, Anna De Luca, Maria Antonietta Margiani, Giulia Vincenzi, Fabrizio Rimondo, Claudia Di Rosa, Fabiana Gregori, Adolfo Varani, Katia Borea, Pier Andrea Serpelloni, Giovanni Marti, Matteo
Copyright Year	2016
Abstract	AKB48 and its fluorinate derivate 5F-AKB48 are two novel synthetic cannabinoids belonging to a structural class with an indazole core structure. They are marketed as incense, herbal preparations or chemical supply for their psychoactive Cannabis-like effects.The present study was aimed at investigating the in vitro and in vivo pharmacological activity of AKB48 and 5F-AKB48 in male CD-1 mice and comparing their in vivo effects with those caused by the administration of Δ9-THC and JWH-018.In vitro competition binding experiments performed on mouse and human CB1 and CB2 receptors revealed a nanomolar affinity and potency of the AKB48 and 5F-AKB48. In vivo studies showed that AKB48 and 5F-AKB48, 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, hyperreflexia and promoted aggressiveness in mice. Moreover, microdialysis study in freely moving mice showed that systemic administration of AKB48 and 5F-AKB48 stimulated dopamine release in the nucleus accumbens. Behavioural, neurological and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM 251.For the first time, the present study demonstrates the overall pharmacological effects induced by the administration of AKB48 and 5F-AKB48 in mice and suggests that the fluorination can increase the power and/or effectiveness of SCBs. Furthermore, this study outlines the potential detrimental effects of SCBs on human health.
Starting Page	3685
Ending Page	3709
Page Count	25
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	233
Issue Number	21-22
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-08-15
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	AKB48 5F-AKB48 JWH-018 Δ9-THC Sensorimotor responses Cannabinoids Synthetic cannabinoids Behavior Microdialysis Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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Effect of the novel synthetic cannabinoids AKB48 and 5F-AKB48 on “tetrad”, sensorimotor, neurological and neurochemical responses in mice. In vitro and in vivo pharmacological studies

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