Abstract
Two drugs, trifluoropentoxypicolinic acid (TFP) and 5-butoxypicolinic acid, which are composed of a picolinic acid skeleton and an alkoxyl group, were studied to determine characteristics of their antihypertensive effect. The study was carried out using normotensive rats and experimental hypertensive rats (DOCA type hypertensive, one-kidney type hypertensive and spontaneous hypertensive), and effects of these drugs were compared with those of fusaric acid (5-butylpicolinic acid), which is known as a hypotensive agent inhibiting dopamine β-hydroxylase. The hypotensive effect of the drugs (10, 30 and 100mg/kg, p.o.) on normotensive rats was weaker than on hypertensive rats. TFP showed a dosedependent hypotensive effect which was not influenced by reserpine pretreatment. Though TFP showed the same inhibitory effect on serum dopamine β-hydroxylase as fusaric acid, it had only approximately 0.5 times the inhibitory activity. However, TFP had a hypotensive effect which was 1.4 times stronger than that of fusaric acid. According to pharmacokinetic analysis based on the determination of blood drug concentration, the transfer rate of fusaric acid from the digestive tract to the blood was much higher than TFP by 1.6×104 times. Moreover, fusaric acid had a 4.5 times greater disappearance rate than TFP. From the above results, first of all, it is supposed that the antihypertensive effect of TFP is related to inhibition of dopamine β-hydroxylase. In addition, it is suggested that prolonged presence of unchanged TFP in the blood increases its immediate depressive effect on the cardiovascular system, thereby causing a strong hypotensive effect.
