N-Docosahexaenoylethanolamine (synaptamide) is structurally similar to the endocannabinoid N-arachidonoylethanolamine (anandamide), but incorporates the omega-3 22:6 fatty acid docosahexaenoic acid (DHA) in place of the omega-6 20:4 fatty acid arachidonic acid (AA). Some brain membrane lipid effects may be mediated via synaptamide. In competition experiments with mouse brain homogenate in vitro, we found that synaptamide was an order-of-magnitude poorer inhibitor of radioactive anandamide hydrolysis than was anandamide itself. Also, enzyme-mediated hydrolysis of synaptamide was observed to occur at a slower rate than for anandamide. We have synthesized synaptamide radiolabeled with carbon-14 in both the ethanolamine ([α,β-¹⁴C₂]synaptamide) and in the DHA ([1-¹⁴C]synaptamide) moieties. The brain penetration, distribution, and metabolism of radiolabeled synaptamide were studied in mice in vivo relative to anandamide, DHA, and AA. Brain uptake of labeled synaptamide was greater than for labeled DHA, consistent with previous studies of labeled anandamide and AA in our laboratory. After administering either isotopomer of radiolabeled synaptamide, radiolabeled phospholipids were found in mouse brain. Pretreatment of mice with PF3845, a potent, specific inhibitor of fatty acid amide hydrolase (FAAH), eliminated formation of labeled phospholipids measured after 15 min, suggesting that synaptamide is hydrolyzed nearly exclusively by FAAH, though it is a poorer substrate for FAAH than anandamide.

N-二十二碳六烯基乙醇胺（synaptamide）在结构上类似于内源性大麻素N-花生四烯酸乙醇胺（anandamide），但掺入了omega-3 22：6脂肪酸二十二碳六烯酸（DHA）代替了omega-6 20：4脂肪酸花生四烯酸（ AA）。某些脑膜脂质效应可能通过突触酰胺介导。在体外小鼠脑匀浆的竞争实验中，我们发现，与安南酰胺本身相比，突触酰胺是放射性安南酰胺水解的数量级差的抑制剂。而且，观察到酶介导的突触酰胺水解发生的速率比anandamide慢。我们已经合成了在乙醇胺（[α，β- ¹⁴C ₂ ] synaptamide）和DHA（[ ^1-14 C ] synaptamide）部分。在小鼠体内研究了放射性标记的突触酰胺的脑渗透，分布和代谢相对于anandamide，DHA和AA。标记的突触酰胺的脑摄取量大于标记的DHA，与我们实验室先前对标记的anandamide和AA的研究一致。施用放射性标记的突触酰胺的任一异构体后，在小鼠脑中发现了放射性标记的磷脂。用PF3845（一种有效的脂肪酸酰胺水解酶抑制剂）进行的小鼠预处理，消除了15分钟后测得的标记磷脂的形成，这表明突触酰胺几乎完全被FAAH水解，尽管FAAH的底物比anandamide差。 。