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Local and systemic phentolamine antagonism of norepinephrine-induced hand vein constriction.

Author(s): Goldberg MJ, Collins JF, Rowe HM, Cerimele BJ

Affiliation(s): Lilly Laboratory for Clinical Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46202, USA.

Publication date & source: 1995-02, J Clin Pharmacol., 35(2):170-5.

Publication type: Clinical Trial; Comparative Study; Randomized Controlled Trial

The dorsal hand vein distention technique has been used to study the effects of alpha-adrenergic receptor antagonists on alpha-agonist-induced venoconstriction. Using this technique, we investigated the dose-effect relationships between different intravenous routes of phentolamine (an alpha-antagonist) administration on norepinephrine (an alpha-agonist)-induced hand vein constriction. Hand vein studies were done on healthy men; each man was studied on up to four occasions. On one occasion for each man, graded doses of phentolamine were infused into a hand vein preconstricted (submaximally) with norepinephrine. The dose of phentolamine producing a half maximal response (ED50) for reversal of venoconstriction, and the maximal reversal were calculated. On the other three occasions (randomly allocated) for each man, graded doses of norepinephrine were infused into a hand vein before and during intravenous infusions of (1) control (vehicle solutions); (2) systemic (other arm vein) phentolamine; and (3) local (hand vein) phentolamine. Systemic and local phentolamine dose ratios (ED50 of norepinephrine during phentolamine, divided by ED50 of norepinephrine before phentolamine; divided by the control dose ratio) were calculated. These studies show that phentolamine (administered directly into a preconstricted hand vein) can completely reverse norepinephrine-induced venoconstriction. Phentolamine, administered by either local or systemic intravenous infusion, induces a significant rightward shift (approximately 10-fold) in responsiveness to norepinephrine-induced venoconstriction. To achieve comparable degrees of alpha-antagonism, however, systemic phentolamine must be administered intravenously at a dose approximately 3,000-fold higher than that of local phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

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