Comparison of the antagonistic activity of tamsulosin and doxazosin at vascular alpha 1-adrenoceptors in humans.
alpha 1-Adrenoceptor blockers such as prazosin and doxazosin are used to treat hypertension as well as benign prostatic hyperplasia (BPH), whereas the new alpha 1-adrenoceptor blocker tamsulosin is used only for BPH and does not reduce blood pressure at the doses used to relax prostatic smooth muscle. In contrast to prazosin, tamsulosin has a higher affinity for prostatic than vascular alpha 1-adrenoceptors in vitro. The functional correlate of this observation in humans is the subject of this study. The alpha 1-adrenoceptor blockade by oral tamsulosin (0.2 mg), doxazosin (1 mg) or placebo on finger tip vascular and dorsal hand venous alpha 1-adrenoceptors stimulated by cold treatment (immersion in ice water) and the alpha 1-adrenoceptor agonist phenylephrine, was thus studied in a 3-way crossover study in eight, healthy, male adults. Finger tip vasoconstriction after cold stimulation was assessed by laser Doppler flowmetry. A linear variable differential transformer was used to assess the drug effect on phenylephrine-induced venoconstriction. All study parameters were assessed at around 2 and 3.5 h after oral intake of doxazosin and tamsulosin respectively. The drug plasma levels were not significantly different. No significant differences were found for blood pressure or heart rate in the three treatments in supine and erect position. The reduction in finger tip blood flow after cold stimulation was significantly smaller after doxazosin treatment (P < 0.01) than after tamsulosin or placebo, whereas there was no significant difference between tamsulosin and placebo treatments. The infusion rate of phenylephrine producing a half-maximum venoconstriction was significantly larger after doxazosin than after tamsulosin (P < 0.05) or placebo (P < 0.01), whereas there was again no significant difference between tamsulosin and placebo treatments. The data suggest that, at doses producing equal plasma levels after single oral doses in human subjects, the blocking activity at vascular alpha 1-adrenoceptors is lower for tamsulosin than for doxazosin.
Harada
K
K
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Ohmori
M
M
Fujimura
A
A
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D003080:Cold Temperature; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides / Q000097:blood / Q000494:pharmacology*; D000077409:Tamsulosin; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; D010656:Phenylephrine; D000077409:Tamsulosin; D017292:Doxazosin