An acute study of the electrophysiological and haemodynamic effects of intravenous UK‐52,046, a novel alpha 1‐adrenoceptor antagonist.

Barin, Edward; Wong, Chih-Shung; Elstob, J; Davies, D. Wyn; Nathan, Anthony W.

doi:10.1111/j.1365-2125.1990.tb03648.x

Cited by 3 publications

(1 citation statement)

References 6 publications

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“…Abanoquil had no apparent effects on surface electrographic intervals or on baroreflex sensitivity. Although the relatively insensitive methodologies in this study cannot exclude an effect on cardiac cellular electrophysiology as has, for example, been found in guinea pig isolated perfused hearts during ischaemia (Flores & Sheridan, 1988), these negative findings are entirely consistent with those reported from more detailed studies (Barin et al, 1990;McKaigue & Harron, 1990).…”

Section: Discussionsupporting

confidence: 88%

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.

Schafers

Elliott

Modesti

et al. 1991

Brit J Clinical Pharma

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3 Despite evidence of substantial oxl-adrenoceptor antagonism abanoquil had no significant effect on blood pressure, supine and erect, but there were small and statistically significant increments in heart rate.4 The degree of ol-adrenoceptor antagonism was related to whole blood concentrations abanoquil: the PD-ratios of phenylephrine pressor responses performed at 1, 6, and 12 h post dosing were significantly correlated with log drug concentrations (r = 0.57 for systolic (P < 0.05) and r = 0.78 for diastolic blood pressure (P < 0.005). 5 In conclusion, abanoquil produced significant oal-adrenoceptor antagonism which was related to circulating drug concentrations. The absence of other significant cardiovascular effects suggests that abanoquil warrants further clinical study as an antiarrhythmic agent.

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Section: Discussionsupporting

confidence: 88%

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.

Schafers

Elliott

Modesti

et al. 1991

Brit J Clinical Pharma

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α-Adrenoceptors

Ruffolo

Hieble

1994

Pharmacology & Therapeutics

122

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Major advances have been made in our understanding of the molecular structure and function of the alpha-adrenoceptors. Many new subtypes of the alpha-adrenoceptor have been identified recently through biochemical and pharmacological techniques and several of these receptors have been cloned and expressed in a variety of vector systems. Currently, at least seven subtypes of the alpha-adrenoceptor have been identified and the molecular structure and biochemical functions of these subtypes are beginning to be understood. The alpha-adrenoceptors belong to the super family of receptors that are coupled to guanine nucleotide regulatory proteins (G-proteins). A variety of G-proteins are involved in the coupling of the various alpha-adrenoceptor subtypes to intracellular second messenger systems, which ultimately produce the end-organ response. The mechanisms by which the alpha-adrenoceptor subtypes recognize different G-proteins, as well as the molecular interactions between receptors and G-proteins, are the topics of current research. Furthermore, the physiological and pathophysiological role that alpha-adrenoceptors play in homeostasis and in a variety of disease states is also being elucidated. These major advances made in alpha-adrenoceptor classification, molecular structure, physiologic function, second messenger systems and therapeutic relevance are the subject of this review.

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Haemodynamic dose‐response effects of UK‐52,046 in ischaemic disease with or without impaired left ventricular function.

Silke

Zezulka

Verma

et al. 1990

Brit J Clinical Pharma

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1 The haemodynamic effects of a new cardioselective postsynaptic a 1-adrenoceptor antagonist UK-52,046, were evaluated in 25 patients with stable coronary disease, with or without impaired left ventricular function. At rest the haemodynamic effects to two doseresponse regimens were determined. In an initial eight patients 0.125, 0.125 and 0.25 ,ug kg-1 were administered peripherally at 15 min intervals; the haemodynamic measurements were determined between 10 to 15 min after each dose. In a further 17 patients, the dose regimen was doubled yielding a cumulative dose-regimen of 0.25, 0.5 and 1.0 ,ug kg-1. The exercise effects were determined by comparison of measurements during 4 min of supine sub-maximal bicycle exercise at a fixed workload before and after drug treatment.2 At rest, the lower dose regimen of UK-52,046 significantly reduced systemic mean arterial blood pressure (-5 mm Hg; P < 0.05) and increased cardiac index (+ 0.21 min-' m-2, P < 0.01). The higher dose regimen of UK-52,046 reduced systemic mean arterial blood pressure (-7 mm Hg; P < 0.01), pulmonary artery occluded pressure (PAOP) (-2 mm Hg, P < 0.01) and vascular resistance index (-314 dyn s cm-5 M2; P < 0.05) with an increase in heart rate (+ 7%, P < 0.05) and cardiac index (+ 0.2 1 min-' m-2, P < 0.05). 3 During dynamic exercise, low dose UK-52,046 did not change the haemodynamics significantly. High dose UK-52,046 reduced systemic mean arterial blood pressure (-5.9 mm Hg, P < 0.01), PAOP (-8.5 mm Hg, P < 0.01), systemic vascular resistance index (-281 dyn s cm-5 m2, P < 0.01) and increased cardiac index (+0.81 min-' m-2, P < 0.01). Comparing haemodynamic response in patients whose initial PAOP > 18 mm Hg with those below did not demonstrate any apparent difference in haemodynamic response related to the presence or absence of left ventricular functional impairment. 4 Thus, UK-52,046 was haemodynamically safe in coronary artery disease; during exercise-induced heart failure beneficial effects on preload and cardiac pumping activity were evident.

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An acute study of the electrophysiological and haemodynamic effects of intravenous UK‐52,046, a novel alpha 1‐adrenoceptor antagonist.

Cited by 3 publications

References 6 publications

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.

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.

α-Adrenoceptors

Haemodynamic dose‐response effects of UK‐52,046 in ischaemic disease with or without impaired left ventricular function.

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