Pressor effect of L-threo-3,4-dihydroxyphenylserine in rats


Department of Pharmacology, Kobe University School of Medicine, Chuo-ku, Kobe 650, Japan


The pressor effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in rats and its decarboxylation in vivo have been examined. On i.v. administration, it produces a slow-onset and long-lasting pressor response, but no significant change in heart rate or e.c.g. The pressor effect was markedly reduced by inhibition of peripheral decarboxylase and by blockade of α-adrenoceptors. The slow-onset and long-acting pressor effect was also evident when the drug was given orally, while intracerebroventricular administration produced a long-lasting decrease in blood pressure. Noradrenaline (NA) concentrations in the plasma were significantly increased by both i.v. and oral administration of L-threo-DOPS. Elevation of plasma NA concentration by L-threo-DOPS given i.v. was suppressed by inhibition of decarboxylase. The plasma concentration of the drug was highest immediately after its i.v. administration. Its pressor effect was enhanced in rats made hypotensive by chemical sympathectomy with 6-hydroxydopamine (6-OHDA), compared with control rats, nevertheless, L-threo-DOPS produced the same increase in plasma NA concentrations in sympathectomized rats as in the controls. These results indicate that L-threo-DOPS is gradually converted to NA by L-aromatic amino acid decarboxylase in vivo. These findings suggest that L-threo-DOPS may be clinically useful as an oral pressor agent for the treatment of certain disorders related to hypotension.