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  • Title: Presynaptic alpha 2-adrenoceptors mediating inhibition of noradrenaline and 5-hydroxytryptamine release in rat cerebral cortex: further characterization as different alpha 2-adrenoceptor subtypes.
    Author: Maura G, Bonanno G, Raiteri M.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1992 Apr; 345(4):410-6. PubMed ID: 1352383.
    Abstract:
    In a previous investigation it was suggested that the alpha 2-adrenoceptors regulating 3H-noradrenaline (3H-NA) release and the alpha 2-heteroreceptors regulating the release of 3H-5-hydroxytryptamine (3H-5-HT) from rat cerebrocortex synaptosomes represent different subtypes of the alpha 2-adrenoceptor in that (-)-mianserin potently blocked the receptors sited on 5-HT terminals but was ineffective at the autoreceptors (Raiteri et al. 1983). In this work a number of alpha 2-adrenoceptor antagonists were tested against NA as an inhibitor of the K+ (15 mmol/l)-evoked release of 3H-NA or 3H-5-HT (in presence of 1 mumol/l desipramine or citalopram, respectively) from superfused rat neocortex synaptosomes. The order of apparent affinity of the antagonists was: idazoxan greater than or equal to ORG 20769 (2-amino-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-thiazole-5-ca rbonitrile (Z)-2-butenedioate (1:1) salt) greater than ORG 20350 (5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2- amine (Z)-2-butenedioate (1:1) salt) greater than or equal to ORG 20091 (5-chloro-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2- amine (Z)-2-butenedioate (2:1) salt) at the alpha 2-autoreceptor and idazoxan greater than or equal to ORG 20769 greater than ORG 20091 much greater than ORG 20350 at the alpha 2-heteroreceptor. Prazosin (1 mumol/l) or AR-C 239 (1 mumol/l) (2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]ethyl]-4,4-dimethyl- 1,3(2H,4H)-isoquinolinedione) were ineffective in both systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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