Stereoselective blockade of alpha-adrenoceptors by berbine derivatives.
The effects of the two enantiomers of berbine (5,6,13,13a-tetrahydro-8H-dibenzo[a,g]quinolizine) and of derivatives obtained by introducing various substitutions on aromatic rings were investigated on alpha 1- or alpha 2-adrenoceptor subtypes. Binding studies carried out on rat cerebral cortex membranes using [3H]prazosin or [3H]yohimbine showed that the affinities of the (+) and (-)enantiomers for alpha 1 and alpha 2 binding sites were different and were differently modified by substitutions added to the berbine nucleus, leading to alpha 1- and alpha 2-selective compounds. Experiments performed on the isolated rat aorta and in pithed rats in vivo demonstrated the alpha-blocking property of berbine derivatives and confirmed the stereoselectivity of the effects of the (+) and (-)enantiomers on alpha 1- and alpha 2-adrenoceptor subtypes.
Schott
C
C
Unité de Pharmacologie Cellulaire et Moléculaire, Université Louis Pasteur, Strasbourg, France.
Tetsi
L
L
Heitz
C
C
Stambach
J F
JF
Jung
L
L
Stoclet
J C
JC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001600:Berberine Alkaloids / Q000494:pharmacology*; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008024:Ligands; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D001600:Berberine Alkaloids; D008024:Ligands; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin