Comparative Study of Cerebrovascular Activity of New Derivatives of N-Arachidonoyl-GABA and GABA Conjugate with Prostaglandin E₂

N-Arachidonoyl-GABA isopropyl ester increased blood flow in the rat cerebral cortex to a greater extent than N-arachidonoyl-GABA in experiments on anesthetized rats subjected to global transient ischemia. The cerebrovascular effect of N-arachidonoyl-GABA isopropyl ester was proposed to involve two mechanisms of action in brain vessels, i.e., on GABA_A receptors and on calcium channels through cannabinoid receptors CB1. Conversely, the isopropyl ester of the GABA conjugate with prostaglandin E₂ under these conditions exhibited cerebrovascular activity to a lesser extent than the GABA conjugate with prostaglandin E₂. The possibility that this ester influenced both GABA_A and prostaglandin receptors of brain vessels was considered. Thus, the structure(activity (cerebrovascular) relationship of the studied compounds was revealed.