Guanfacine inhibits excitatory amino acid release from rat cerebral cortex through a non-adrenergic mechanism
Uhlén, S.; Näsström, J.; Post, C.; Wikberg, J.E.
Pharmacology and Toxicology 65(5): 357-361
1989
ISSN/ISBN: 0901-9928 PMID: 2695915 Document Number: 336656
The effect of guanfacine on the release of excitatory amino acids from rat cerebral cortex slices was assessed after preloading the slices with 3H-D-aspartate. It was found that guanfacine dose-dependently inhibited the veratridine stimulated release of the excitatory amino acid analogue; the ED50 of guanfacine being 6.4.+-.2.3 .mu.M (mean .+-. S.E.M.) and the veratradine stimulated efflux being completely abolished at about 48 .mu.M of guanfacine. Guanfacine also inhibited the veratridine stimulated release of endogenous aspartate and glutamate with similar potency to the inhibition of 3H-D-aspartate efflux. The inhibitory effect of guanfacine on the veratridine stimulated 3H-D-aspartate efflux was neither affected by high concentrations of the .alpha.2-adrenoceptor blocker idazoxan nor by high concentrations of the .alpha.1-adrenoceptor blocker prazosin. It is concluded that guanfacine inhibits the neural excitatory amino acid release in the rat cortex by a novel non-.alpha.2/.alpha.1-adrenergic mechanism.