Novel halogenated derivates of JWH-018: Behavioral and binding studies in mice

NEUROPHARMACOLOGY

卷:95

Article

Vigolo, A.¹  Ossato, A.¹  Trapella, C.^4,5  Vincenzi, F.⁶  Rimondo, C.⁷  Seri, C.⁷  Varani, K.⁶  Serpelloni, G.⁷  Marti, M.^1,2,3,4 

[1] Univ Ferrara, Dept Life Sci & Biotechnol SVeB, I-44121 Ferrara, Italy

[2] Ctr Neurosci, Naples, Italy

[3] Ist Nazl Neurosci, Naples, Italy

[4] Presidency Council Ministers, Drug Policies Dept, Collaborat Ctr Italian Natl Early Warning Syst, Milan, Italy

[5] Univ Ferrara, Dept Chem & Pharmaceut Sci, I-44121 Ferrara, Italy

[6] Univ Ferrara, Dept Med Sci, I-44121 Ferrara, Italy

[7] Presidency Council Ministers, Drug Policies Dept, Italian Natl Early Warning Syst, Milan, Italy

关键词: Delta(9)-THC;    JWH-018;    JWH-018 Br;    JWH-018 Cl;    CB1 receptor;    Synthetic cannabinoids;   

DOI  :  10.1016/j.neuropharm.2015.02.008

来源: Elsevier

【 摘 要 】

JWH-018 is a synthetic CB1 and CB2 agonist illegally marketed as products named Spice or herbal blend for its psychoactive effects which are much higher than those produced by cannabis. In the last year, the European Monitoring Centre for Drugs and Drug Addiction reported to the Italian National Early Warning System the seizure of plant material containing new halogenated derivatives of JWH-018 (JWH-018 Cl and JWH-018 Br). The present study aimed to investigate the in vitro and in vivo activity of these two new synthetic cannabinoids in mice. In vitro competition binding experiments performed on mouse and human CB1 receptors revealed a high affinity and potency of the halogenated compounds. Synthetic cannabinoids (0.01-6 mg/kg i.p.) impaired motor activity and induced catalepsy in mice and their effects were more severe with respect to those evoked by Delta(9)-THC. Moreover, they increased the mechanical and thermal pain threshold and induced a marked hypothermia. It is interesting to note that whereas high doses of JWH-018 cause seizures, myoclonia and hyperreflexia, the halogenated compounds, in particular JWH-018Br, were less effective. Behavioral and neurological changes were prevented by the selective CBI receptor antagonist AM 251. These data demonstrate for the first time that JWH-018 Cl and JWH-018 Br act similarly to JWH-018 while inducing less convulsive episodes and myoclonias. These data support the hypothesis that the halogenated compounds may have been introduced onto market to produce similar intoxicating effects as JWH-018 while causing less side effects. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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