Alpha 2-adrenoceptor blocking properties of idazoxan stereoisomers: stereoselectivity for presynaptic alpha 2-adrenoceptors.
The alpha 2-adrenoceptor blocking properties of idazoxan enantiomers were evaluated at pre- and postsynaptic level. The antagonism of the two idazoxan stereoisomers was assessed, at presynaptic level, by their ability to antagonize clonidine at the alpha 2-adrenoceptors regulating noradrenaline release. The antagonist (+)-idazoxan showed an affinity towards the alpha 2-autoreceptors 40 times higher than that showed by (-)-idazoxan. Binding studies revealed (+)-idazoxan to be 7-8 times more potent than (-)-idazoxan in inhibiting the p-[3H]aminoclonidine binding. These results indicate a different affinity of alpha 2-adrenoceptors for the two idazoxan stereoisomers, thus suggesting that the alpha 2-adrenoceptors located pre- and postsynaptically may be of two stereochemically different subtypes.
Martire
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M
Department of Pharmacology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
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D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D019329:Idazoxan; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D004146:Dioxanes; D004147:Dioxins; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan