Antagonistic activity of tamsulosin against human vascular alpha1-adrenergic receptors.
OBJECTIVE
To elucidate the vascular effect of tamsulosin hydrochloride (INN, tamsulosin), a selective alpha1A-adrenergic receptor antagonist, in humans, we examined the alpha1-adrenergic receptor antagonistic activity against blood vessels after oral intake of recommended and higher doses of the drug and evaluated the relation between its plasma concentrations and the effect.


METHODS
Nine healthy men ranging in age from 21 to 38 years received tamsulosin (0.2 mg or 0.6 mg) or lactate capsule as a control after breakfast in a randomized crossover fashion. Seven hours after administration, their fingertip vasoconstrictor response to contralateral hand cooling and vasoconstrictor response of the dorsal hand vein to phenylephrine were examined, and blood samples for the measurement of plasma drug concentration were obtained.


RESULTS
The fingertip vasoconstrictor response was significantly reduced and the infusion rate of phenylephrine producing a half-maximal constriction was significantly increased by 0.6 mg tamsulosin but not by 0.2 mg tamsulosin. There were significant positive correlations between plasma drug concentrations and the changes of these parameters.


CONCLUSIONS
These results suggest that although the alpha1-adrenergic receptor-blocking effect of tamsulosin on blood vessels is relatively small, it is clearly correlated with plasma drug concentration and a higher dose of the drug could cause systemic adverse effects.
Harada
K
K
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Kawaguchi
A
A
Ohmori
M
M
Fujimura
A
A
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000077409:Tamsulosin; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; D010656:Phenylephrine; D000077409:Tamsulosin