Methylphenidate increases heart rate, blood pressure and plasma epinephrine in normal subjects

doi:10.1016/0024-3205(84)90568-X

Life Sciences

Volume 34, Issue 18, 30 April 1984, Pages 1707-1711

https://doi.org/10.1016/0024-3205(84)90568-X Get rights and content

Abstract

Following an intravenous infusion of methylphenidate (0.3mg/kg) there were significant increases in plasma epinephrine, heart rate, systolic and diastolic pressure, but there was no change in plasma norepinephrine. This pattern of response differs from that seen with D-amphetamine or caffeine.

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Cited by (29)

Effects of methylphenidate hydrochloride on the cardiovascular system in vivo and in vitro: A safety pharmacology study
2009, Journal of Pharmacological and Toxicological Methods
Citation Excerpt :
It has already been reported that MPH may elevate BP at therapeutic dosage levels in humans (Ballard et al., 1976; Brown & Sexson, 1989; Kelly et al., 2005; Volkow et al., 2003; Wang et al., 1999; Wilens et al., 2005). Moreover, MPH-induced elevation of BP, and dopamine levels in the striatum were correlated with increases in the plasma epinephrine levels in humans as well (Joyce, Nicholls, & Donald, 1984; Kelly et al., 2005; Volkow et al., 2003). Therefore, it is likely that MPH elevates BP by similar mechanisms in animals and humans.
We examined the effects of methylphenidate hydrochloride (MPH) on the cardiovascular system using in vivo and in vitro study methods in accordance with the ICH-S7B guideline.
MPH was orally administered at doses of 3, 10 and 30 mg/kg to unrestrained conscious dogs implanted with a telemetry transmitter and attached with body surface electrodes, and electrocardiogram (ECG) leads. The QTcF interval was determined while heart rate (HR), and blood pressure (BP) were measured. Action potentials in isolated guinea-pig papillary muscle and the rapid component of the delayed rectifier potassium current (I_Kr) in HEK-293 cells stably transfected with hERG were also investigated at concentrations of 0.1, 0.3 and 1 µg/mL (0.37, 1.1 and 3.7 µmol/L) of MPH.
No ECG changes were observed except for a shortening of the QT interval due to a shortening of the RR interval at the maximum dose tested, 30 mg/kg. The only observed change was an elevation of BP in dogs at the dose of 30 mg/kg, which is approximately 10 times higher than the maximum therapeutic dose for use in children with attention deficit hyperactivity disorder (ADHD). Neither APD prolongation nor I_Kr inhibition was observed by MPH in the in vitro studies up to the maximum concentration tested, 1 µg/mL (3.7 µmol/L), which is approximately 34 times higher than the clinically attainable unbound plasma MPH concentrations in children with ADHD.
These results suggest that it is unlikely that MPH affects ventricular repolarization processes at the therapeutically recommended dose levels in patients with ADHD.
Supraventricular tachycardia associated with methylphenidate treatment in a heart transplant recipient
2005, Psychosomatics
Biological challenges in obsessive compulsive disorder
1988, Progress in Neuropsychopharmacology and Biological Psychiatry
Swinson, Richard P. and Joffe, Russell T.: Biological Challenges in Obsessive Compulsive Disorders. Prog. Neuro — Psychopharmacol. and Biol. Psychiat. 1988, $12$ :269–275
- 1.
  1. Obsessive compulsive disorder and affective disorder have been investigated by means of various biological challenges.
- 2.
  2. Total sleep deprivation and methylphenidate challenge were used to determine the effects on a group of subjects with obsessive compulsive disorder.
- 3.
  3. The findings of a lack of response to total sleep deprivation and methylphenidate in obsessive compulsive patients contrasts with the findings in affective disorder patients.
- 4.
  4. The findings are more consistent with those in studies of panic disorder.
- 5.
  5. The relationship of obsessive compulsive disorder to affective and anxiety disorder may be elucidated by further studies.
Endocrine and behavioral responses to methylphenidate in normal subjects
1986, Biological Psychiatry
Methylphenidate (0.3 mg/kg) was administered intravenously to 20 normal subjects. Behavioral responses varied considerably among individuals. Both cortisol and growth hormone showed significant increases (p < 0.001). The adrenocorticotrophic hormone (ACTH) response seemed insufficient to explain the increase in cortisol. For men only, the increase in cortisol correlated positively with the increase in epinephrine (r = 0.77, p < 0.05) and correlated negatively with baseline cortisol (r = −0.70, p < 0.05), with increase in growth hormone (r = −0.70, p < 0.05), and with the increase in “energy” (r = −0.83, p < 0.01). The growth hormone response varied between the sexes, and for men, the growth hormone correlated with both an increase in “energy” (r = 0.70, p < 0.05) and “friendliness” (r = 0.68, p < 0.05). For all subjects, baseline heart rate correlated with the increase in “energy” (r = −0.69, p < 0.002). In a separate study, six male subjects received, on different occasions, saline and a lower dose of methylphenidate. Together, these studies show that the increases in cortisol, growth hormone, and epinephrine, and the decrease in prolactin are dose-dependent.
Physostigmine reduces the plasma cortisol response to methylphenidate in normal subjects
1986, Journal of Psychiatric Research
Six healthy male subjects were studied to determine whether the reduced plasma cortisol response to methylphenidate observed in depressed patients could be reproduced in normal subjects by pretreatment with physostigmine. Indeed, physostigmine was found to mimic this effect. The finding raises the possibility that increased cholinergic rather than decreased adrenergic activity could explain the blunted cortisol response to stimulants reported in depressed patients. Physostigmine also enhanced the growth hormone rise and prolactine decline, and limited the increase in heart rate following methylphenidate administration.
Personalized Connectome Mapping to Guide Targeted Therapy and Promote Recovery of Consciousness in the Intensive Care Unit
2020, Neurocritical Care

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Methylphenidate increases heart rate, blood pressure and plasma epinephrine in normal subjects

Abstract

Europ. J. Pharmacol.

Europ. J. Pharmacol.

Life Sciences

Metabolism

Europ. J. Pharmacol.

J. Pharm. Pharmacol.

life Sciences

N.E.J.M.