title: Behavioural and pharmacological characterization of a novel cannabinomimetic adamantane-derived indole, APICA, and considerations on the possible misuse as a psychotropic spice abuse, in C57bl/6J mice.
abstract: The novel adamantane derivative APICA (N-(adamantan-1-yl)-1-pentyl-1H-indole-3-carboxamide) was recently identified as a cannabinomimetic indole of abuse. Despite its novel structure, APICA recalls cannabinomimetic indoles, such as representative member JWH-018. In present study, the effects of APICA (1-3mg/kg, i.p.) were tested in C57BL/6J mice, in the Tetrad task which includes the assessment of: body temperature; locomotor activity and behavioural reactivity; nociception; motor coordination; declarative memory. Furthermore, pre-treatment with the CB1 antagonist AM251 (3mg/kg, i.p.) or the CB2 antagonist AM630 (3mg/kg, i.p.) was carried out to characterize APICA activity. Our results show that APICA was able to dose-dependently decrease locomotor activity and behavioural reactivity in the open field, whereas only the highest dose was able to induce hypothermia, analgesia, motor incoordination and recognition memory impairment, with respect to vehicle (p<0.01; p<0.001). The pretreatment with the CB1 antagonist AM251 elicited an increase in body temperature, total distance travelled in the open field, latency to fall down in the Rotarod, and a decrease in tail flick latency (p<0.05; p<0.01). On the other hand, pretreatment with AM630 did not induced significant differences on APICA effects. This study supports preliminary reports on APICA cannabinomimetic properties, extending its detrimental effects on cognitive function. Moreover, these properties can be attributed to the CB1 receptor activity, indicating APICA as a selective CB1 receptor agonist.
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, Palermo, Italy. Electronic address: carla.cannizzaro@unipa.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Cannizzaro
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, Palermo, Italy.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Malta
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, Palermo, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Argo
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, Palermo, Italy; BioNeC, University of Palermo, Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Brancato
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli, 25, Milano 20133, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Roda
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli, 25, Milano 20133, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Casagni
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli, 25, Milano 20133, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fumagalli
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli, 25, Milano 20133, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Valoti
authors.affiliation: Institute of Legal Medicine and Insurance, University of Macerata, Via Don Minzoni 9, Macerata 62100, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Froldi
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care, University of Palermo, Palermo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Procaccianti
authors.affiliation: Department of Pharmaceutical Sciences, University of Milan, Via Mangiagalli, 25, Milano 20133, Italy.
authors.forename: Veniero
authors.initials: V
authors.lastname: Gambaro
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015198:Designer Drugs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005554:Forensic Medicine; D007191:Indazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000187:drug effects
chemical_list: D002186:Cannabinoids; D015198:Designer Drugs; D007191:Indazoles; C000606545:N-(1-adamantyl)-1-pentylindazole-3-carboxamide; D000218:Adamantane
keywords: APICA; CB1 agonist; New psychotropic substances; Synthetic cannabinoid