Acute effects of flosequinan (BTS 49465) in untreated moderate to severe hypertension.
Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acting vasodilator that should cause relatively less reflex tachycardia, was given in a single oral dose of 200 mg to 10 untreated patients with moderate to severe hypertension. Flosequinan caused a fall in blood pressure (BP) from 181/116 +/- 7/4 to 161/102 +/- 5/4 mm Hg (P < 0.05). The proportional decrease of mean arterial pressure (MAP) was 14.6% (P < 0.01). Together with the decrease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/min occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insignificantly (NS) from 3.7 +/- 0.6 to 5.5 +/- 1.5 ml/100 ml/min together with a small decrease in forearm vascular resistance from 47 +/- 7 to 39 +/- 7 arbitrary units (NS). Forearm venous distensibility remained stable around 0.03% mm Hg (NS). Neurohormonal parameters showed the consequences of systemic vasodilation: noradrenaline rose from 1.25 +/- 0.10 to 2.88 +/- 0.34 nmol/l (P < 0.01), adrenaline from 0.16 +/- 0.03 to 0.35 +/- 0.10 nmol/l (NS), plasma renin activity from 2.33 +/- 0.46 to 3.27 +/- 0.73 ng/ml/h (P < 0.05) and aldosterone from 14.31 +/- 2.47 to 26.3 +/- 8.02 ng/ml (P < 0.05). The serum concentrations of flosequinan and its major metabolite were within the therapeutic limits. Nine patients experienced minor side-effects such as headache, nausea and palpitations. We conclude that flosequinan has hypotensive efficacy with signs of systemic counter-regulatory mechanisms but without a clear forearm vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Janssen
M C
MC
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Smits
P
P
Reyenga
J
J
Thien
T
T
D000284:Administration, Oral; D000328:Adult; D000450:Aldosterone / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011804:Quinolines / Q000627:therapeutic use*; D015363:Quinolones / Q000097:blood; D012083:Renin / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use*
D011804:Quinolines; D015363:Quinolones; D014665:Vasodilator Agents; D000450:Aldosterone; C047316:flosequinan; C047317:flosequinoxan; D012083:Renin; D009638:Norepinephrine; D004837:Epinephrine