Modafinil Elicits Sympathomedullary Activation

Taneja, Indu; Diedrich, André; Black, Bonnie K.; Byrne, Daniel W.; Paranjape, Sachin Y.; Robertson, David

doi:10.1161/01.hyp.0000158267.66763.63

Cited by 58 publications

(48 citation statements)

References 34 publications

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“…Modafinil also appeared to increase blood pressure, although only the change in supine systolic blood pressure reached statistical significance. This small increase is in agreement with previous reports on the effect of modafinil on blood pressure (200 mg: Makris et al, 2004;Turner et al, 2003;Samuels et al, 2006;4200 mg: Caldwell et al, 2000;Rush et al, 2002;Makris et al, 2004;Taneja et al, 2005). In addition, when clonidine and modafinil were administered together, modafinil antagonized the effect of clonidine on supine systolic blood pressure.…”

Section: Discussionsupporting

confidence: 92%

“…The autonomic effects of modafinil were in opposite directions to those of clonidine, consistent with sympathetic activation, which in turn may be related to the activation of the LC (Hou et al, 2005;Taneja et al, 2005). Thus, modafinil caused a significant increase in pupil diameter at the highest luminance level, in agreement with a previous report using a 200-mg dose of modafinil (Hou et al, 2005(Hou et al, , 2007.…”

Section: Discussionsupporting

confidence: 89%

“…The doses were chosen on the basis of the current literature (modafinil: Taneja et al, 2005;clonidine: Morley et al, 1991;Bitsios et al, 1996;Phillips et al, 2000c, d). The time required to attain peak plasma concentrations (t MAX ) of clonidine and modafinil after the ingestion of single doses is approximately 2 h (modafinil: Wong et al, 1998;clonidine: Lowenthal et al, 1988), and the time course of the sessions was designed to ensure peak plasma concentrations of the drugs at the start of the post-treatment testing.…”

Section: Drugsmentioning

confidence: 99%

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Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Samuels

Hou

Langley

et al. 2007

Neuropsychopharmacol

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A sudden loud sound evokes an electromyographic (EMG) response from the orbicularis oculi muscle in humans together with an auditory evoked potential (AEP) and an increase in skin conductance (SC). Startle responses are inhibited by weak prepulses (prepulse inhibition, (PPI)) and may also be modified by the level of alertness. We compared the sedative drug clonidine and the alerting drug modafinil on sound-evoked EMG, AEP, and SC responses, on the PPI of these responses and on level of arousal and autonomic functions. Sixteen healthy male volunteers participated in four weekly sessions (clonidine 0.2 mg, modafinil 400 mg, their combination, placebo) in a double-blind, cross-over, balanced design. Responses were evoked by sound pulses of 115 and 85 dB (PPI) for 40 ms and recorded conventionally. Level of alertness, autonomic functions (pupil diameter, blood pressure, heart rate, salivation, temperature) and the plasma levels of the hormones prolactin, thyroid-stimulating hormone and growth hormone were also measured. Data were analyzed with analysis of variance with multiple comparisons. Both prepulses and clonidine attenuated all three startle responses and modafinil antagonized clonidine's effects on the EMG and AEP responses. None of the drugs affected PPI. Clonidine showed sedative and sympatholytic effects, and modafinil showed alerting and sympathomimetic effects. In conclusion, startle responses were susceptible not only to PPI but also to the level of arousal. Keywords: acoustic startle response; auditory evoked potential; skin conductance; prepulse inhibition; clonidine; modafinil INTRODUCTIONThe startle response involves rapid involuntary contractions of facial and skeletal musculature in response to a sudden intense stimulus. In the case of the acoustic startle response, this reaction occurs in response to a sudden loud sound and is measurable in humans as an electromyographic (EMG) response from the orbicularis oculi muscle (eyeblink startle response). This response is believed to be mediated via a pathway below the level of the diencephalon consisting of between three and five central synapses, originating from the sensory receptors and terminating on the motor neurons, where the principal relay is the caudal pontine reticular nucleus (Davis et al, 1982; for review, see Yeomans and Frankland, 1996;Koch, 1999). In addition to this muscular response, changes in electroencephalographic (EEG) activity can be observed in response to the auditory stimulus, and these changes are termed auditory evoked potentials (AEP). In particular, the N1/P2 component of the AEP is measurable following the presentation of the acoustic startle stimulus (for examples, see Abduljawad et al, 1999Abduljawad et al, , 2001 Phillips et al, 2000a, b;Graham et al, 2001Graham et al, , 2004Scaife et al, 2005Scaife et al, , 2006. Both the muscular and the AEP responses are fast responses; longer-latency responding to the startle stimulus can be observed in autonomic activity, in particular in sympathetically mediated skin conductance...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Drugsmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of the Acoustic Startle Response by the Level of Arousal: Comparison of Clonidine and Modafinil in Healthy Volunteers

Samuels

Hou

Langley

et al. 2007

Neuropsychopharmacol

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“…Other medication classes that may worsen blood pressure control include sympathomimetic compounds such as decongestants and certain diet pills, amphetamine-like stimulants, modafinil 39 , and oral contraceptives. Glucocorticoids, such as prednisone, induce sodium and fluid retention and can result in significant increases in blood pressure.…”

Section: Drug-related Causesmentioning

confidence: 99%

Resistant Hypertension: Diagnosis, Evaluation, and Treatment

Calhoun¹,

Jones²,

et al. 2008

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Abstract-Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder.

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“…However, the contribution of sympathetic activation by modafinil cannot be entirely excluded. In healthy subjects, modafinil has been found to increase the velocity of the sympathetically mediated darkness reflex (Hou et al 2005), and there is independent evidence demonstrating the sympathetic activating effect of modafinil (Taneja et al 2005). A better way to dissect the relative contributions of the sympathetic and parasympathetic systems in modafinil-induced mydriasis in OSA might be peripheral monocular sympatholysis with dapiprazole eyedrops, as in the paradigm developed by Giakoumaki et al (2005).…”

Section: Discussionmentioning

confidence: 99%