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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A study of the selectivity and potency of rauwolscine, RX 781094 and RS 21361 as antagonists of alpha-1 and alpha-2 adrenoceptors.

In a comparative study using various in vivo and in vitro models, the alpha-1/alpha-2 adrenoceptor blocking potencies and selectivities were quantitatively assessed for the purported alpha-2 adrenoceptor selective antagonists rauwolscine, RX 781094 and RS 21361. In pithed normotensive rats, RX 781094 showed direct agonist activity at postjunctional alpha-1 and alpha-2 adrenoceptors and had an indirect tachycardic effect. RS 21361 exhibited but minor actions on diastolic pressure and did not influence heart rate. Rauwolscine, RX 781094 and RS 21361 caused rightward parallel displacements of the log dose-response curve to the increase in diastolic pressure of methoxamine (alpha-1 agonist) and B-HT 920 (alpha-2 agonist) as well as to the B-HT 920-induced reduction in stimulation-evoked tachycardia. Schild plots afforded straight lines with slopes not significantly different from unity. Rauwolscine was more potent than RX 781094 in blocking these alpha-2 adrenoceptors in vivo, whereas both compounds were equipotent at alpha-1 adrenoceptors. RS 21361 possessed moderate in vivo blocking potencies at either subtype. All three antagonists had high blocking selectivity for alpha-2 adrenoceptors in vivo. Rauwolscine was found about 25 times more selective than RX 781094 and 2 times more selective than RS 21361. RX 781094 was approximately 3 times more effective than rauwolscine in antagonizing the centrally mediated alpha-2 adrenoceptor-induced hypotension and sedation of clonidine in rats and mice, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. A study of the selectivity and potency of rauwolscine, RX 781094 and RS 21361 as antagonists of alpha-1 and alpha-2 adrenoceptors. Timmermans, P.B., Qian, J.Q., Ruffolo, R.R., van Zwieten, P.A. J. Pharmacol. Exp. Ther. (1984) [Pubmed]
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