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Cardiovascular actions of a new selective postjunctional α.‐adrenoceptor antagonist, SK&F 104856, in normotensive and hypertensive dogs
Author(s) -
Hieble J. Paul,
Nichols Andrew J.,
Fredrickson Todd A.,
DePalma P. Dennis,
Ruffolo Robert R.,
Brooks David P.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09090.x
Subject(s) - prazosin , rauwolscine , blood pressure , medicine , endocrinology , contractility , antagonist , chemistry , receptor
1 SK&F 104856 (2‐vinyl‐7‐chloro‐3,4,5,6‐tetrahydro‐4‐methylthieno[4,3,2ef][3]benzazepine) is a novel postjunctional α. 1 ‐ and α. 2 ‐adrenoceptor antagonist. 2 SK&F 104856 as well as prazosin and SK&F 86466 reduced blood pressure in the anaesthetized normotensive dog. 3 SK&F 86466 and rauwolscine but not SK&F 104856 or prazosin, produced a marked increase in myocardial contractility which corresponds with their ability to block prejunctional α. 2 ‐adrenoceptors. 4 Intravenous or oral administration of SK&F 104856 resulted in dose‐dependent antihypertensive responses in 1‐kidney, 1‐clip (1‐K, 1‐C) Goldblatt hypertensive dogs with baseline blood pressure of approximately 140 mmHg. At 0.1 and 1 mg kg −1 , i.v., mean arterial blood pressure fell by 11 ± 5 and 23 ± 5 mmHg, respectively. At 3 and 10 mg kg −1 , p.o., blood pressure fell by 9 ± 3 and 22 ± 5 mmHg, respectively. At 10 mg kg −1 , p.o., the antihypertensive effect of SK&F 104856 was still evident at 4 h. 5 The data indicate that SK&F 104856 shows selectivity in vivo for postjunctional versus prejunctional α.‐adrenoceptors and is a potent and long‐acting antihypertensive agent in 1‐K, 1‐C Goldblatt hypertensive dogs.