title: Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma.
abstract: BACKGROUND
  The cardiovascular effects of psychostimulant drugs (methylphenidate, amphetamine, cocaine) have been mostly associated with their noradrenergic effects. However, there is some evidence that dopaminergic effects are involved in the cardiovascular actions of these drugs. Here, we evaluated this association in humans.
  
  
  METHODS
  Positron emission tomography (PET) and [(11)C]raclopride, a dopamine (DA) D2 receptor radioligand that competes with endogenous DA for occupancy of the D2 receptors, were used to measure changes in brain DA after different doses of intravenous methylphenidate in 14 healthy subjects. Cardiovascular (heart rate and blood pressure) and catecholamine (plasma epinephrine and norepineprhine) responses were determined in parallel to assess their relationships to methylphenidate-induced changes in brain DA.
  
  
  RESULTS
  Methylphenidate administration significantly increased heart rate, systolic and diastolic blood pressures and epinephrine concentration in plasma. The increases in blood pressure were significantly correlated with methylphenidate-induced increases of DA in striatum (r>0.78, P<0.001) and of plasma epinephrine levels (r>0.82, P<0.0005). In turn methylphenidate-induced DA increases in striatum were correlated with increases of epinephrine in plasma (r=0.85, P<0.0001). Subjects in whom methylphenidate did not increase DA had no change in blood pressure or in plasma epinephrine concentration.
  
  
  CONCLUSIONS
  These results are consistent with the hypothesis that methylphenidate-induced increases in blood pressure are in part due to its central dopaminergic effects. They also suggest that methylphenidate's pressor effects may be in part mediated by DA-induced increases in peripheral epinephrine.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. volkow@bnl.gov
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: S John
authors.initials: SJ
authors.lastname: Gatley
authors.forename: Andrew
authors.initials: A
authors.lastname: Gifford
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.forename: Christopher
authors.initials: C
authors.lastname: Wong
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Pappas
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000097:blood / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008774:Methylphenidate / Q000097:blood / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013268:Stimulation, Chemical; D014055:Tomography, Emission-Computed
chemical_list: D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine