Noradrenergic activity in anticipatory nausea

Two studies were conducted to examine the hypothesis that noradrenergic activity is a cause of the anticipatory nausea associated with cancer chemotherapy. In the first study concentrations of plasma 3-methoxy-4- hydroxyphenyl-glycol (MHPG) on day 1 of cycle 5 of initial chemotherapy were significantly higher in patients with than without anticipatory nausea. To determine whether elevated MHPG reflected a clinically significant causative role for noradrenergic activity in anticipatory nausea, we conducted a randomized, double-blind, placebo-controlled, crossover trial of clonidine for anticipatory nausea. At a dose of clonidine that produced significant side effects and reductions of plasma MHPG, anticipatory nausea was improved only marginally. These studies do not support a causative role for noradrenergic activity in anticipatory nausea that can be reduced by clonidine with an acceptable therapeutic index.