Effect of alpha 1-adrenoceptor antagonists, prazosin and urapidil, on a finger skin vasoconstrictor response to cold stimulation.
OBJECTIVE
Cold stimulation causes a finger skin vasoconstrictor response, which is regulated by stimulation of alpha-adrenergic receptors and is reduced by administration of prazosin. The purpose of this study was to investigate, using a laser Doppler flowmeter, whether the decrease in the finger skin vasoconstrictor response to cold stimulation produced by administration of two different alpha 1-adrenoceptor antagonists, prazosin and urapidil, was correlated with the corresponding plasma drug concentration, and whether this method could be used to evaluate the relative potency of these alpha 1-adrenoceptor antagonists in human subjects.


METHODS
In thirteen healthy male subjects (20-42 y), finger tip skin blood flow was measured during cold stimulation before and 1, 2, 3, 6, and 9 h after administration of placebo, prazosin (1 mg) or urapidil (60 mg).


RESULTS
Both prazosin and urapidil significantly decreased the vasoconstrictor response to cold stimulation. The degree of the decrement in the response indicated by the reduction ratio was significantly correlated with the plasma concentration of prazosin and urapidil. The alpha 1-adrenoceptor blocking activity of prazosin estimated by the regression lines was about 130-times more potent than that of urapidil.


CONCLUSIONS
These findings suggest that the cold stimulation response of finger skin vasoconstriction may be used to evaluate the relative alpha 1-adrenoceptor blocking potency of drugs.
Harada
K
K
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Ohashi
K
K
Fujimura
A
A
Kumagai
Y
Y
Ebihara
A
A
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D003080:Cold Temperature / Q000009:adverse effects; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011224:Prazosin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; C015568:urapidil; D011224:Prazosin