Erowid References Database
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U'Prichard DC, Greenberg DA, Snyder SH.
“Binding Characteristics of a Radiolabeled Agonist and Antagonist at Central Nervous System Alpha Noradrenergic Receptors”.
Mol.Pharmacol.. 1977;13:454-73.
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Abstract
The binding characteristics of agonists and antagonists to CNS n-noradrenergic membrane receptors were studied. Homogenates of adult male Sprague-Dawley rat whole brains or brains minus cerebellum were incubated with 3H-clonidine (CD; Boehr.Ingelheim; 4 nM) or 3H-WB-4101 (Ward-Blenkinsop, 0.22 nM) in the presence of (-)-noradrenaline (NA; Sterling Winthrop; 10 or 100 pM) or tests drugs (see below). Some rats were pretreated with 6-hydroxydopamine (6-OHDA; 250mcg intraventricularly) on 2 days. Endogenous NA levels and 3H-NA uptake were determined. Binding of 3H-ligands was saturable with KD values of 5.8 nM and 0.48 nM for 3H-CD and 3H-WB-4101, respectively. Catecholamines inhibited ligand binding in the potency order adrenaline NA isoprenaline, corresponding to peripheral a-receptor activation. Competition for binding was stereospecific ((-)phenylethanolamines (+)isomers). p-Hydroxylation or N methylation increased the affinity for CD-binding sites. Imidazolines competed for both sites; sympathomimetics preferentially inhibited CD binding. a-Antagonists inhibited WB-4101 binding. Ergotalkaloids reduced binding of both ligands. p-Antagonists, muscarinic anticholinergics, antihistamines, antibypertensives and MAOI were poor inhibitors. Tricyclic antidepressants benzotropine, promethazine, antipsychotics and haloperidol had high affinity for WB-4101 sites. Binding was highest in the cerebral cortex and lowest in the cerebellum. 6-OHDA reduced NA levels by 80%, NA uptake by 67% and reduced ligand binding.
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