1.
Flosequinan (BTS 49 465, 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) a novel arteriovenous dilator agent was orally effective in conscious renal hypertensive dogs and normotensive cats. The hypotensive potency of
flosequinan was approximately ten times less than that of
hydralazine in renal hypertensive dogs, 10 mg kg-1 and 20 mg kg-1
flosequinan causing similar falls in mean blood pressure to 1 mg kg-1 and 3 mg kg-1
hydralazine respectively. In normotensive cats, 5 mg kg-1
flosequinan caused similar falls to 0.5 and 1.0 mg kg-1
hydralazine. The onset of hypotensive effect after
flosequinan appeared to be slightly slower than after
hydralazine in the dog and slightly faster than
hydralazine in the cat. 2. The degree of
tachycardia and increase in plasma
renin activity (PRA) for equivalent falls in mean blood pressure in both species was significantly less for
flosequinan than for
hydralazine (P less than 0.05). 3. In normotensive dogs,
flosequinan, 10 and 20 mg kg-1 orally, caused a small but non-significant increase in
sodium and
chloride excretion and had little effect on urine volume whereas
hydralazine, 1 and 3 mg kg-1 orally, caused a marked retention of
sodium and
chloride ions and a reduction in urine volume (P less than 0.01). 4. Neither
flosequinan, 10 mg kg-1 orally, nor
hydralazine 1 mg kg-1 orally, affected either glomerular filtration rate measured as
creatinine clearance or effective renal plasma flow measured as
p-aminohippuric acid clearance in normotensive dogs. 5. The lesser degree of
tachycardia and increase in plasma
renin activity together with a lack of
sodium retaining activity associated with
flosequinan suggest that this agent may have potential advantages over existing
therapy as an
antihypertensive in man.