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. 1992 Apr;105(4):992–996. doi: 10.1111/j.1476-5381.1992.tb09090.x

Cardiovascular actions of a new selective postjunctional alpha-adrenoceptor antagonist, SK&F 104856, in normotensive and hypertensive dogs.

J P Hieble 1, A J Nichols 1, T A Fredrickson 1, P D DePalma 1, R R Ruffolo Jr 1, D P Brooks 1
PMCID: PMC1908712  PMID: 1354539

Abstract

1. SK&F 104856 (2-vinyl-7-chloro-3,4,5,6-tetrahydro-4- methylthieno[4,3,2ef][3]benzazepine) is a novel postjunctional alpha 1- and alpha 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 alpha 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 alpha-adrenoceptors and is a potent and long-acting antihypertensive agent in 1-K, 1-C Goldblatt hypertensive dogs.

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Selected References

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