1. The effects of
fluparoxan, an alpha 2-adrenoceptor antagonist, on the pharmacodynamic changes induced by
clonidine were investigated in this placebo-controlled, double-blind, two-period, cross-over study in 16 healthy male volunteers (aged 19 to 44 years). 2. Subjects received either
fluparoxan or placebo, twice-daily for 5 1/2 days (11 doses). One hour after the first and last dose of each treatment period,
clonidine (200 micrograms) was infused intravenously over 5 min. 3. Indices of
clonidine-mediated pharmacodynamic responses (
growth hormone secretion,
bradycardia,
hypotension,
xerostomia and sedation) were taken before and after
clonidine infusion.
Growth hormone secretion was assessed by quantifying serum
growth hormone concentrations; sedation was assessed by both visual analogue scales (VAS) and by a visual psychomotor response meter, measuring critical flicker fusion (CFF). 4. The majority of subjects reported minor adverse events such as
lethargy,
headache and dry mouth following
clonidine infusion. All adverse events were likely to be related to
clonidine, as they occurred consistently between treatment groups.
Fluparoxan has, however, in previous studies been reported to cause
headache and
light-headedness. 5. Prior to the
clonidine infusion,
fluparoxan caused small but statistically significant increases in systolic blood pressure (4 mm Hg) and salivary flow (approximately 30%) after both single and repeated doses. A small increase in heart rate (2 beats min-1) was seen after a single dose which was also statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)