title: Berbanes: search for novel alpha-2 adrenoceptor antagonists.
abstract: We have previously described the alpha-2 adrenoceptor antagonist properties of berbanes and its stereoisomers. Of the compounds studied CH-38083 (2,3-methylenedioxy-11-betahydroxyalloberbane) has been selected for further analysis based upon its high affinity and selectivity for central and peripheral alpha-2 adrenoceptors. Structure activity relationship study revealed that the aromatic ring with its substituents at C-2 and C-3 positions, the nitrogen atom, the hydroxy group at C-11 position and the methoxycarbonyl group at C-12 position are important for the binding of the berbanes to the alpha-2 adrenoceptors. Using alloberbane derivatives for characterization of the alpha-2 adrenoceptors it was speculated that xylazine sensitive alpha-2 adrenoceptors in the rat vas deferens and in the guinea-pig ileum are similar, whereas xylazine sensitive and noradrenaline sensitive alpha-2 adrenoceptors of the guinea-pig ileum may belong to different subtypes. Correlation studies indicated that modification of the molecular structure of the alloberbanes can lead to either increased or decreased alpha-2 adrenoceptor antagonists activity without parallel changes in the alpha-1 adrenoceptor antagonist potency. The low affinity of CH-38083 for other receptor populations (muscarinic, histamine, dopamine receptors) makes this compound attractive for investigation of alpha-2 adrenoceptor-mediated neural processes in the central nervous system and periphery.
authors.affiliation: Department of Pharmacology, Postgraduate Medical School, Hungarian Academy of Sciences, Budapest.
authors.forename: L G
authors.initials: LG
authors.lastname: Harsing
authors.forename: G
authors.initials: G
authors.lastname: Lonart
authors.forename: S E
authors.initials: SE
authors.lastname: Vizi
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D000470:Alkaloids; D001600:Berberine Alkaloids; D001599:Berberine; C048886:7,8-(methylenedioxy)-14-hydroxyberbane