Effects of atipamezole--a selective alpha-adrenoceptor antagonist--on cardiac parasympathetic regulation in human subjects.
1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of alpha2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml(-1) at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15-0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (+/-SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml(-1). 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.
Penttilä
J
J
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
Kaila
T
T
Helminen
A
A
Anttila
M
M
Karhuvaara
S
S
Huhtala
S
S
Scheinin
H
H
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D010656:Phenylephrine
D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D010656:Phenylephrine