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. 1991 Nov;32(5):599–604. doi: 10.1111/j.1365-2125.1991.tb03958.x

Studies with abanoquil (UK-52,046) a novel quinoline alpha 1-adrenoceptor antagonist: I. Effects on blood pressure, heart rate and pressor responsiveness in normotensive subjects.

R F Schafers 1, H L Elliott 1, C A Howie 1, J L Reid 1
PMCID: PMC1368637  PMID: 1683249

Abstract

1. Abanoquil (UK 52,046) is a novel, quinoline-derivative, alpha 1-adrenoceptor antagonist which, on the basis of animal studies, possesses antiarrhythmic activity at doses which have little or no effect on blood pressure. 2. In two placebo-controlled, double-blind, crossover studies the alpha 1-adrenoceptor antagonist activity (phenylephrine pressor responses) and the effects on blood pressure and heart rate (in the presence and absence of concomitant beta-adrenoceptor blockade) have been investigated in healthy, normotensive subjects following the intravenous administration (i.v.) of abanoquil. 3. In the first study, abanoquil at a dose of 0.4 micrograms kg-1 i.v. (as a bolus or by increments) produced significant alpha 1-adrenoceptor antagonism (with rightward shifts of more than two-fold in the phenylephrine pressor dose-response curves) but no significant effects on supine or erect blood pressure and heart rate. 4. In the second study, a dose of 0.5 micrograms kg-1 i.v. had no significant effect on supine or erect blood pressure but pre-treatment with atenolol promoted a small fall in erect blood pressure without causing significant orthostatic hypotension. 5. In conclusion, significant alpha 1-adrenoceptor antagonism without marked reflex tachycardia or profound postural hypotension suggest that abanoquil has a different haemodynamic profile from that of 'classical' peripheral alpha 1-adrenoceptor antagonists.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brückner R., Mügge A., Scholz H. Existence and functional role of alpha 1-adrenoceptors in the mammalian heart. J Mol Cell Cardiol. 1985 Jul;17(7):639–645. doi: 10.1016/s0022-2828(85)80063-8. [DOI] [PubMed] [Google Scholar]
  2. Elliott H. L., McLean K., Sumner D. J., Meredith P. A., Reid J. L. Immediate cardiovascular responses to oral prazosin--effects of concurrent beta-blockers. Clin Pharmacol Ther. 1981 Mar;29(3):303–309. doi: 10.1038/clpt.1981.40. [DOI] [PubMed] [Google Scholar]
  3. Elliott H. L., Meredith P. A., Sumner D. J., McLean K., Reid J. L. A pharmacodynamic and pharmacokinetic assessment of a new alpha-adrenoceptor antagonist, doxazosin (UK33274) in normotensive subjects. Br J Clin Pharmacol. 1982 May;13(5):699–703. doi: 10.1111/j.1365-2125.1982.tb01439.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elliott H. L., Vincent J., Meredith P. A., Reid J. L. Relationship between plasma prazosin concentration and alpha-antagonism in humans: comparison of conventional and rate-controlled (Oros) formulations. Clin Pharmacol Ther. 1988 May;43(5):582–587. doi: 10.1038/clpt.1988.77. [DOI] [PubMed] [Google Scholar]
  5. Manning A. S., Hearse D. J. Reperfusion-induced arrhythmias: mechanisms and prevention. J Mol Cell Cardiol. 1984 Jun;16(6):497–518. doi: 10.1016/s0022-2828(84)80638-0. [DOI] [PubMed] [Google Scholar]
  6. Schafers R. F., Elliott H. L., Meredith P. A., Miller S. H., Reid J. L. Studies with abanoquil (UK-52,046) a novel quinoline alpha 1-adrenoceptor antagonist: II. Duration of action, pharmacokinetics and concentration-effect relationships in normotensive subjects. Br J Clin Pharmacol. 1991 Nov;32(5):605–610. doi: 10.1111/j.1365-2125.1991.tb03959.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Seideman P., Grahnén A., Haglund K., Lindström B., von Bahr C. Prazosin dynamics in hypertension: relationship to plasma concentration. Clin Pharmacol Ther. 1981 Oct;30(4):447–454. doi: 10.1038/clpt.1981.187. [DOI] [PubMed] [Google Scholar]
  8. Sumner D. J., Elliott H. L., Reid J. L. Analysis of the pressor dose response. Clin Pharmacol Ther. 1982 Oct;32(4):450–458. doi: 10.1038/clpt.1982.188. [DOI] [PubMed] [Google Scholar]
  9. Sumner D. J., Elliott H. L. The pressor dose-response in clinical cardiovascular pharmacology. Br J Clin Pharmacol. 1987 May;23(5):499–503. doi: 10.1111/j.1365-2125.1987.tb03084.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Uprichard A. G., Harron D. W., Wilson R., Shanks R. G. Effects of the myocardial-selective alpha 1-adrenoceptor antagonist UK-52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs. Br J Pharmacol. 1988 Dec;95(4):1241–1254. doi: 10.1111/j.1476-5381.1988.tb11761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Vincent J., Elliott H. L., Meredith P. A., Reid J. L. Doxazosin, an alpha 1-adrenoceptor antagonist: pharmacokinetics and concentration-effect relationships in man. Br J Clin Pharmacol. 1983 Jun;15(6):719–725. doi: 10.1111/j.1365-2125.1983.tb01556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Vincent J., Elliott H. L., Meredith P. A., Reid J. L. Doxazosin, an alpha 1-adrenoceptor antagonist: pharmacokinetics and concentration-effect relationships in man. Br J Clin Pharmacol. 1983 Jun;15(6):719–725. doi: 10.1111/j.1365-2125.1983.tb01556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wilber D. J., Lynch J. J., Montgomery D. G., Lucchesi B. R. Alpha-adrenergic influences in canine ischemic sudden death: effects of alpha 1-adrenoceptor blockade with prazosin. J Cardiovasc Pharmacol. 1987 Jul;10(1):96–106. doi: 10.1097/00005344-198707000-00014. [DOI] [PubMed] [Google Scholar]

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