title: Noradrenergic activity in anticipatory nausea.
abstract: 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.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, MD 21287.
authors.forename: J H
authors.initials: JH
authors.lastname: Fetting
authors.forename: M E
authors.initials: ME
authors.lastname: Stefanek
authors.forename: V R
authors.initials: VR
authors.lastname: Sheidler
authors.forename: J D
authors.initials: JD
authors.lastname: Elsworth
authors.forename: S
authors.initials: S
authors.lastname: Piantadosi
authors.forename: R H
authors.initials: RH
authors.lastname: Roth
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003000:Clonidine / Q000008:administration & dosage; D003214:Conditioning, Classical / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D009369:Neoplasms / Q000188:drug therapy* / Q000523:psychology; D009638:Norepinephrine / Q000502:physiology*; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology; D014840:Vomiting, Anticipatory / Q000503:physiopathology* / Q000523:psychology
chemical_list: D011941:Receptors, Adrenergic; D008734:Methoxyhydroxyphenylglycol; D003000:Clonidine; D009638:Norepinephrine