title: 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.
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 CB1and CB2receptors 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 CB1receptor 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.
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, via Fossato di Mortara 17-19, 44121, Ferrara, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Canazza
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, via Fossato di Mortara 17-19, 44121, Ferrara, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ossato
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Fantinati
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: De Luca
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Margiani
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.affiliation: Department of Diagnostic and Public Health, University of Verona, Verona, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rimondo
authors.affiliation: Department of Scientific Investigation (RIS), Carabinieri, 00191, Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Di Rosa
authors.affiliation: Department of Scientific Investigation (RIS), Carabinieri, 00191, Rome, Italy.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Gregori
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.affiliation: Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.affiliation: U.R.I.To.N., Forensic Toxicology Unit, Department of Health Science, University of Florence, Florence, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Serpelloni
authors.affiliation: Department of Life Sciences and Biotechnology (SVeB), University of Ferrara, via Fossato di Mortara 17-19, 44121, Ferrara, Italy. m.marti@unife.it.|Center for Neuroscience and Istituto Nazionale di Neuroscienze, ᅟ, Italy. m.marti@unife.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Marti
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002188:Cannabis; D002375:Catalepsy / Q000139:chemically induced*; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012021:Reflex, Abnormal / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D007191:Indazoles; D007211:Indoles; C000606545:N-(1-adamantyl)-1-pentylindazole-3-carboxamide; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C103505:AM 251; D013759:Dronabinol; C552597:1-pentyl-3-(1-naphthoyl)indole; D000218:Adamantane; C000603150:N-(1-adamantyl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide; D004298:Dopamine
keywords: 5F-AKB48; AKB48; Behavior; Cannabinoids; JWH-018; Microdialysis; Sensorimotor responses; Synthetic cannabinoids; Δ9-THC