title: Neurotolerability of gadobenate dimeglumine. Evaluation of brain dopamine concentration in freely moving rats by microdialysis.
abstract: OBJECTIVE
  Magnetic resonance imaging with contrast agents (CAs) is a procedure currently used for the diagnosis of neurologic pathologies. These pathologies are often characterized by blood-brain barrier disruptions, which determines a direct contact between CA and brain tissue. For this reason, an accurate assessment of neurotolerability is useful for the development of new CAs. The present study was designed to evaluate the neurotolerability of a new CA for MRI, gadobenate dimeglumine, employing a neurochemical method. The effect of gadobenate dimeglumine on the striatal levels of neurotransmitters was determined. In particular, the brain concentrations of dopamine and dopamine metabolites, 3,4-dihydroxyphenylacetic and homovanillic acid, were measured using microdialysis, after the direct application of gadobenate dimeglumine into the rat corpus striatum. Gadopentetate dimeglumine and gadoteridol were employed as reference compounds.
  
  
  METHODS
  A microdialysis probe for brain extracellular fluid sampling and a stainless-steel cannula for CA application were chronically inserted into the right corpus striatum of rats. All CAs were administered at a dose of 5.4 nmol/rat. Dopamine and metabolite concentrations were analyzed using high-performance liquid chromatography.
  
  
  RESULTS
  Gadobenate dimeglumine did not induce any significant changes in the extracellular levels of dopamine or dopamine metabolites up to 2 hours after administration. Gadoteridol produced similar results. Gadopentetate dimeglumine caused a moderate but not significant increase in dopamine levels throughout the duration of the experiments.
  
  
  CONCLUSIONS
  Gadobenate dimeglumine directly administered into the corpus striatum of freely moving rats did not affect the dopaminergic system. This result demonstrates the safety of gadobenate dimeglumine under the experimental conditions used, thus confirming previous behavioral and electrophysiologic findings.
authors.affiliation: Milano Research Centre, Bracco SpA, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: La Noce
authors.forename: V
authors.initials: V
authors.lastname: Frigeni
authors.forename: I
authors.initials: I
authors.lastname: Filatori
authors.forename: A
authors.initials: A
authors.lastname: Danieli
authors.forename: P
authors.initials: P
authors.lastname: Tirone
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003287:Contrast Media / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D019786:Gadolinium DTPA / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017551:Microdialysis; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D015102:3,4-Dihydroxyphenylacetic Acid; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium; D019786:Gadolinium DTPA; D004298:Dopamine; D006719:Homovanillic Acid