Dose-dependent alpha 1-adrenoceptor antagonist activity of the anti-arrhythmic drug, abanoquil (UK-52,046), without reduction in blood pressure in man.
1. The dose-dependency of the alpha 1-adrenoceptor antagonist activity of the anti-arrhythmic abanoquil (UK-52,046) was investigated in 10 healthy male subjects who received serially increasing infusions of phenylephrine before and 2, 4, 8, 12, 24 and 48 h after single oral doses of abanoquil 0.25, 0.5 and 1 mg and placebo in a double-blind randomised manner. 2. The doses of phenylephrine required to increase systolic BP by 20 mm Hg (PS20) were calculated using a quadratic fit to the individual dose-response curves. 3. Abanoquil 0.25, 0.5 and 1 mg increased the PS20 in a dose-dependent manner with effects which were maximal at 2 to 8 h and lasted for 24 to 48 h (P less than 0.05). Maximal dose ratios were: abanoquil 0.25 mg 2.0 +/- 0.9, 0.5 mg 2.4 +/- 1.3, 1 mg 3.4 +/- 1.1. 4. No change occurred in supine BP but a small increase (P less than 0.01) occurred in supine HR 8 h post-dosing (64 +/- 9, 58 +/- 6 beats min-1 for abanoquil 1 mg and placebo respectively). 5. Therefore abanoquil 0.25, 0.5 and 1 mg showed dose-dependent alpha 1-adrenoceptor antagonist activity with no effect on supine BP.
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
T C
TC
Tham
S
S
Guy
R G
RG
Shanks
D W
DW
Harron
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000634:Aminoquinolines / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D016683:Supine Position; D044005:Tetrahydroisoquinolines
D000317:Adrenergic alpha-Antagonists; D000634:Aminoquinolines; D000889:Anti-Arrhythmia Agents; D044005:Tetrahydroisoquinolines; D010656:Phenylephrine; C058534:abanoquil