MDMB-CHMICA induces thrashing behavior, bradycardia, and slow pressor response in a CB1- and CB2-receptor-dependent manner in conscious rats
MDMB-CHMICA induces thrashing behavior, bradycardia, and slow pressor response in a CB1- and CB2-receptor-dependent manner in conscious rats
复制标题
DOI：
10.1007/s11419-018-0405-1
复制
发表时间：
2018-07-01
影响因子：
2.2
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
--
作者：
Maeda, Hideyuki;Nagashima, Erika;Yoshida, Ken-ichi
MDMB-CHMICA是一种新的合成大麻素（SC），自2014年以来作为娱乐性药物的成分而流行。关于药物中毒的报道越来越多，表现出多种心血管、精神和神经症状。MDMB-CHMICA中毒后猝死和意外死亡与精神障碍有关的报道也有所增加，但其机制尚不清楚。方法在清醒大鼠外周注射MDMB-CHMICA，观察MDMB-CHMICA的作用。对其他SC的心血管反应已被证明仅被大麻素受体-1（CB 1）拮抗剂抑制。然而，MDMB-CHMICA诱导的心动过缓不仅被CB 1拮抗剂AM 281抑制，而且被CB 2拮抗剂AM 630抑制。与其他SC不同，MDMB-CHMICA诱导平均血压逐渐升高，CB 1和CB 2拮抗剂略微增强。对于第一次，我们证明了MDMB-CHMICA诱导的颠簸hypermobile行为的CB 1和CB 2受体依赖的方式，以下僵住样hypomobilitybehaviors.Conclusions这种意想不到的反应MDMB-CHMICA可能有助于解释的机制与其使用相关的突然死亡和事故。
Purpose MDMB-CHMICA, a new synthetic cannabinoid (SC), has become prevalent since 2014 as an ingredient of recreational drugs. Reports on intoxication due to the drug have been increasing, which show diverse cardiovascular, psychiatric, and neuronal symptoms. Reports on sudden death and accidental death related to psychiatric disorders in MDMB-CHMICA intoxication have also increased, but the underlying mechanisms are largely unknown.Methods As there has been no experimental study on the drug, we investigated the effects of peripheral injection of MDMB-CHMICA in conscious rats.Results MDMB-CHMICA induced rapid bradycardia and a slow pressor response. Cardiovascular responses to other SCs have been shown to be inhibited only by cannabinoid receptor-1 (CB1)-antagonists. However, the MDMB-CHMICA-induced bradycardia was inhibited not only by a CB1-antagonist, AM281, but also by a CB2-antagonist, AM630. Unlike other SCs, MDMB-CHMICA induced a gradual increase in mean blood pressure, which was marginally enhanced by the CB1- and CB2-antagonists. For the first time, we demonstrated that MDMB-CHMICA induces a thrashing hypermobile behavior in a CB1- and CB2-receptor-dependent manner, following catalepsy-like hypomobile behavior.Conclusions This unexpected response to MDMB-CHMICA may help explain the mechanisms underlying the sudden deaths and accidents associated with its use.