(+)-Cyclazosin, a selective alpha1B-adrenoceptor antagonist: functional evaluation in rat and rabbit tissues.
To shed light on the discrepancy between reported binding and functional affinity and selectivity at alpha(1b/B)-adrenoceptors, the antagonist (+)-cyclazosin was reinvestigated in rat and rabbit tissues. It displayed a competitive antagonism at alpha(1A) and alpha(1D)-adrenoceptors of rat prostatic vas deferens and aorta with pA(2) values 7.75 and 7.27, respectively. In rabbit thoracic aorta (+)-cyclazosin competitively antagonized noradrenaline-induced contractions at alpha(1B)-adrenoceptors with a pA(2) value of 8.85, whereas its affinity at alpha(1L)-adrenoceptors was markedly lower (pA(2) = 6.75-7.09). In conclusion, these data confirmed that (+)-cyclazosin is a selective alpha(1B)-adrenoceptor antagonist also in functional assays, showing 13- and 38-fold selectivity for the alpha(1B)-adrenoceptor over alpha(1A)- and alpha(1D)-subtypes, respectively. Furthermore, (+)-cyclazosin displayed a significant selectivity for alpha(1B)-adrenoceptors relative to the alpha(1L)-subtype.
Marucci
Gabriella
G
Department of Chemical Sciences, University of Camerino, Italy.
Angeli
Piero
P
Buccioni
Michela
M
Gulini
Ugo
U
Melchiorre
Carlo
C
Sagratini
Gianni
G
Testa
Rodolfo
R
Giardinà
Dario
D
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; C547721:Adra1d protein, rat; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; D011810:Quinoxalines; D018340:Receptors, Adrenergic, alpha-1; C080462:cyclazosin; C051731:chlorethylclonidine; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine