Effects of the novel D2-dopaminergic agonist ropinirol on supine resting and stimulated circulatory and neuroendocrine variables in healthy volunteers.
Ropinirol (SK&F 101468) is a novel drug characterized preclinically as a potent and selective D2-dopaminergic agonist. In the present study the effects of acute doses of 0.4, 0.8 and 1 mg were profiled in eight healthy male volunteers, using a placebo-controlled cross-over study design with incremental dosing. The drug was found to cause mild nausea and postural faintness at the highest dose in one subject. There were no further relevant clinical events, and the postural responses at 200 and 360 min after dosing remained in general well maintained, with the exception of a slight reduction of standing systolic blood pressure. The drug furthermore was found to reduce serum prolactin levels; the magnitude and duration of this effect were dose-related. The drug tended to reduce the noradrenaline responses to 5 min isometric handgrip testing (30% of maximal strength) at 165 min after dosing, and the noradrenaline responses to 3 min immobile standing at 200 min after dosing. The drug also tended to blunt the venous plasma dopamine responses to 3 min cold pressor test (90 min after dosing) and to standing at 200 min after dosing. These changes are concluded to be compatible with the assumed peripheral D2-dopaminergic actions of the drug.
de Mey
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C
SK&F-Institute for Applied Clinical Pharmacology, Göttingen, Fed. Rep. of Germany.
Enterling
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D
Meineke
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I
Brendel
E
E
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003080:Cold Temperature; D015259:Dopamine Agents / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007537:Isometric Contraction; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects*; D011187:Posture; D011388:Prolactin / Q000097:blood; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2
D002395:Catecholamines; D015259:Dopamine Agents; D007211:Indoles; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C046649:ropinirole; D011388:Prolactin