Guanfacine inhibits excitatory amino acid release from rat cerebral cortex through a non-adrenergic mechanism.
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 microM (mean +/- S.E.M.) and the veratradine stimulated efflux being completely abolished at about 48 microM 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.
Uhlén
S
S
Department of Pharmacology, Umeå University, Sweden.
Näsström
J
J
Post
C
C
Wikberg
J E
JE
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001341:Autonomic Nervous System / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004146:Dioxanes / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology*; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014701:Veratridine / Q000494:pharmacology
D000596:Amino Acids; D004146:Dioxanes; D005971:Glutamates; D006146:Guanidines; D010648:Phenylacetates; D001224:Aspartic Acid; D016316:Guanfacine; D014701:Veratridine; D011224:Prazosin; D019329:Idazoxan