Comparison of the behavioral responses induced by phenylalkylamine hallucinogens and their tetrahydrobenzodifuran (FLY) and benzodifuran (DragonFLY) analogs

NEUROPHARMACOLOGY

卷:144

Article

Halberstadt, Adam L.^1,2  Chatha, Muhammad¹  Stratford, Alexander³  Grill, Matthias⁴  Brandt, Simon D.⁵ 

[1] Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA

[2] VA San Diego Healthcare Syst, Res Serv, 3350 La Jolla Village Dr, San Diego, CA 92161 USA

[3] Synex Synthet BV, Karveelweg 20, NL-6222 NH Maastricht, Netherlands

[4] Lipomed AG, Fabrikmattenweg 4, CH-4144 Arlesheim, Switzerland

[5] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Byrom St, Liverpool L3 3AF, Merseyside, England

关键词: 5-HT2A receptor;    Psychedelics;    Head twitch;    New psychoactive substance;    NPS;    2C-B-DragonFLY;    3C-B-FLY;   

DOI  :  10.1016/j.neuropharm.2018.10.037

来源: Elsevier

【 摘 要 】

In recent years, rigid analogs of phenylalkylamine hallucinogens have appeared as recreational drugs. Examples include 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)ethan-1-amine (2C-B-FLY) and 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane (Bromo-DragonFLY, DOB-DFLY). Although some rigid compounds such as DOB-DFLY reportedly have higher potency than their non-rigid counterparts, it is not clear whether the same is true for 2C-B-FLY and other tetrahydrobenzodifurans. In the present study, the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of 2,5-dimethoxy-4-bromoamphetamine (DOB) and its a-desmethyl homologue 2,5-dimethoxy-4-bromophenethylamine (2C-B), as well as their benzodifuranyl and tetrahydrobenzodifuranyl analogs, in C57BL/6J mice. DOB (ED50 = 0.75 mu mol/kg) and 2C-B (ED50 = 2.43 mu mol/kg) induced the HTR. The benzodifurans DOB-DFLY (ED50 = 0.20 mu mol/kg) and 2C-B-DFLY (ED50 = 1.07 mu mol/kg) had significantly higher potency than DOB and 2C-B, respectively. The tetrahydrobenzodifurans DOB-FLY (ED50 = 0.67 mu mol/kg) and 2C-B-FLY (ED50 = 1.79 mu mol/kg), by contrast, were approximately equipotent with their non-rigid counterparts. Three novel tetrahydrobenzodifurans (2C-I-FLY, 2C-E-FLY and 2C-EF-FLY) were also active in the HTR assay but had relatively low potency. In summary, the in vivo potency of 2,5-dimethoxyphenylalkylamines is enhanced when the 2- and 5-methoxy groups are incorporated into aromatic furan rings, whereas potency is not altered if the methoxy groups are incorporated into dihydrofuran rings. The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. The high potency of DOB-DFLY is probably linked to the presence of two structural features (a benzodifuran nucleus and an alpha-methyl group) known to enhance the potency of phenylalkylamine hallucinogens.

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