Quantitative and qualitative analysis of the pressor effects of levonordefrin

Levonordefrin, a common alternative to levoepinephrine as a vasoconstrictor in dental local anesthetic preparations, is usually used in fivefold higher concentrations, and, as such, is generally considered equivalent to epinephrine. We used anesthetized dogs that had autonomic reflexes blocked by mecamylamine to reevaluate the cardiovascular actions of intravenously administered nordefrin with respect to those of epinephrine and norepinephrine over a 100-fold dose range (0.1-10.0 micrograms/kg). Epinephrine caused a significantly greater pressor effect than nordefrin only at the highest dose studied; at low to moderate doses there was no significant difference between the two drugs. Blockade of alpha-adrenoceptors with phentolamine attenuated the peak pressor effects of all three agents. The epinephrine dose-response curve was suppressed more than the curves for norephinephrine and nordefrin, which were not significantly different from each other. Nordefrin was indistinguishable qualitatively from norepinephrine in that neither agent showed any evidence of beta 2-adrenoceptor vasodilation as seen with epinephrine. These findings suggest that nordefrin resembles norepinephrine rather than epinephrine in the receptor profile through which it produces its cardiovascular effects, and that the true potency difference between nordefrin and epinephrine with respect to pressor activity may be somewhat less than the fivefold difference commonly assumed.