Inhibitors of the anandamide transporter as analgesic agents

Abstract

SUMMARY OF THE INVENTION It has now been found that certain analogs of anandamide are potent inhibitors of transport of anandamide across cell membranes. The transport inhibitor does not activate the cannabinoid receptors or inhibit anandamide hydrolysis per se but instead prevents anandamide reuptake thereby prolonging the level of the undegraded anandamide. Previously, cannabinoid drugs were targeted toward cannabiniod receptors and amidase enzymes. The anandamide transport inhibitor of the present invention targets activity of the anandamide transporter. The inhibitors are amide and ester analogs of anandamide and exhibit the tail, central and head pharmacophore portions represented by Structural Formula I X—Y—Z   (I) wherein tail portion X is a fatty acid chain remnant, central portion Y is an amide or ester radical and head portion Z is selected form the group consisting of hydrogen, alkyl, hydroxy alkyl, aryl, hydroxy aryl, heterocyclic and hydroxy heterocyclic radicals. The novel inhibitors of the present invention, when tested in vitro, inhibit accmulation of anandamide in rat cortical neurons and astrocytes and enhance various effects of anandamide administration both in vitro and in vivo. The vasodepressor responses are significantly potentiated and prolonged by the transport inhibitors. Thus, the inhibitors are believed to be effective drugs for the treatment of cardivascular diseases and blood pressure disorders.

Dependencies are inferred from the claim text.