ACUTE EFFECTS OF FLOSEQUINAN (BTS-49465) IN UNTREATED MODERATE TO SEVERE HYPERTENSION

Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolo ne), a recently developed 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 mea n arterial pressure (MAP) was 14.6% (P < 0.01). Together with the decr ease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/m in occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insign ificantly (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 co nsequences 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 +/- 0.4 6 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 flo sequinan 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 efficac y with signs of systemic counter-regulatory mechanisms but without a c lear forearm vasodilation. Particularly the venous dilation, claimed i n normotensives, could not be established in hypertensives.