Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

被引：48

作者：

Breuer, Aviva ^{[1
]}

Haj, Christeene G. ^{[1
]}

Fogaca, Manoela V. ^{[2
]}

Gomes, Felipe V. ^{[2
]}

Silva, Nicole Rodrigues ^{[2
]}

Pedrazzi, Joao Francisco ^{[3
]}

Del Bel, Elaine A. ^{[4
]}

Hallak, Jaime C. ^{[3
]}

Crippa, Jose A. ^{[3
]}

Zuardi, Antonio W. ^{[3
]}

Mechoulam, Raphael ^{[1
]}

Guimaraes, Francisco S. ^{[2
]}

机构：

[1] Hebrew Univ Jerusalem, Fac Med, Inst Drug Res, Jerusalem, Israel

[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pharmacol, Sao Paulo, Brazil

[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Neurosci & Behav, Sao Paulo, Brazil

[4] Univ Sao Paulo, Sch Odontol Ribeirao Preto, Dept Morphol Physiol & Pathol, Sao Paulo, Brazil

来源：

PLOS ONE | 2016年 / 11卷 / 07期

基金：

巴西圣保罗研究基金会;

关键词：

MARBLE-BURYING BEHAVIOR; ELEVATED PLUS-MAZE; PREPULSE INHIBITION; ANIMAL-MODELS; ENDOCANNABINOID SYSTEM; ANXIETY DISORDERS; 5-HT1A RECEPTORS; HASHISH; INVOLVEMENT; DISRUPTION;

D O I：

10.1371/journal.pone.0158779

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.

引用

页数：19

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