Anandamide, an endogenous ligand for central cannabinoid receptors, is
released from neurons on depolarization and rapidly inactivated. Anan
damide inactivation is not completely understood, but it may occur by
transport into cells or by enzymatic hydrolysis. The compound N-(4-hyd
roxyphenyl)arachidonylamide (AM404) was shown to inhibit high-affinity
anandamide accumulation in rat neurons and astrocytes in vitro, an in
dication that this accumulation resulted from carrier-mediated transpo
rt. Although AM404 did not activate cannabinoid receptors or inhibit a
nandamide hydrolysis, it enhanced receptor-mediated anandamide respons
es in vitro and in vivo, The data indicate that carrier-mediated trans
port may be essential for termination of,the biological effects of ana
ndamide, and may represent a potential drug target.