Abstract
Rationale
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 [11C]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.
Discussion
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.
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Acknowledgements
This research was supported in part by the U.S. Department of Energy under contract DE-ACO2–76CH00016 and NIDA grants DA09490 and DA06278. We wish to thank David Schlyer, for Cyclotron operations; Donald Warner for PET operations; Colleen Shea, Robert MacGregor, Victor Garza, Richard Ferrieri and Payton King for radiotracer preparation and analysis; Thomas P Cooper for methylphenidate plasma analysis and Noelwah Netusil and Pauline Carter for patient care.
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Volkow, N.D., Wang, GJ., Fowler, J.S. et al. Cardiovascular effects of methylphenidate in humans are associated with increases of dopamine in brain and of epinephrine in plasma. Psychopharmacology 166, 264–270 (2003). https://doi.org/10.1007/s00213-002-1340-7
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DOI: https://doi.org/10.1007/s00213-002-1340-7