SK&F 86466, a novel alpha-adrenolytic drug: effects on heart rate, blood pressure, and neuroendocrine function in supine resting position and in response to postural and cold stimulation in normal humans.

SK&F 86466 is a novel alpha-adrenoceptor blocking drug shown in preclinical profiling to have relative selectivity for the pre- and postjunctional alpha 2-adrenoreceptor. In the present clinical study, the effects of single oral doses of 10, 25, and 50 mg SK&F 86466 on supine and stimulated circulatory and neuroendocrine function were assessed in eight normal subjects studied in a placebo-controlled balanced cross-over design with the drugs administered in double-blind fashion. SK&F 86466 caused a dose-related increase in stimulated (postural and cold challenge) and supine plasma norepinephrine (NE) concentrations. This increase was associated with an increase in supine heart rate (HR) and plasma renin activity and orthostatically stimulated HR, with little increase in systolic blood pressure (SBP) and no increase in diastolic blood pressure (DBP). Assuming that no changes occurred in catecholamine clearance, SK&F 86466 thus appeared to have a prejunctional alpha 2-adrenoreceptor blocking effect, which was countered by a post-junctional alpha-adrenoreceptor blocking effect at the level of the resistance vessels, whereas this latter effect did not alter the pressor responses to cold and postural challenge.

RCT Entities:   Population Interventions Outcomes