Drug interactions and vasoconstrictors used in local anesthetic solutions

This study examined widely advertised interactions between sympathomimetic amine vasoconstrictors currently used in dental local anesthetic solutions and MAO inhibitors (phenelzine, 5 mg/kg), phenothiazines (chlorpromazine, 2 mg/kg), and tricyclic antidepressants (desipramine, 2 mg/kg). Twelve greyhound dogs premedicated with morphine and anesthetized with urethane and alpha-chloralose were prepared for physiologic recordings. During a control period, the dogs received bolus injections of epinephrine, norepinephrine, and levonordefrin sufficient to construct log-linear dose-response curves for each agent. Commercial anesthetic solutions, with and without the vasoconstrictors, were also used. The dose-response curves were then reproduced 1 hour after the administration of a drug interactant. Cardiovascular responses were not influenced by the coadministration of local anesthetics or by the prior administration of phenelzine. Chlorpromazine ameliorated pressor responses to norepinephrine and levonordephrin and reversed the hypertensive effect of high-dose epinephrine. Desipramine significantly increased vasoconstrictor potencies, particularly those of levonordefrin and norepinephrine, which were multiplied more than sixfold.