Intensity dependence of the cortical auditory evoked potentials as a surrogate marker of central nervous system serotonin transmission in man

Demonstration of a central effect for the 5HT(1B/1D) agonist zolmitriptan (311C90, Zomig®)

A. Proietti-Cecchini, J. Áfra, J. Schoenen

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

As shown in animal studies, 5HT(1B/D) agonists can inhibit activity in the trigeminal nucleus caudalis, which may be advantageous for their antimigraine effect. To demonstrate a possible central nervous system (CNS) action of these compounds in man we studied their effect on the intensity dependence of the cortical auditory evoked potentials (IDAPs), thought to be inversely related to central serotonergic transmission. An amplitude/stimulus intensity function (ASF) slope was computed in healthy volunteers and migraine patients between attacks before and 2 h after oral 311C90 (zolmitriptan 'Zomig') 10 mg (n=14), 311C90 5 mg (n=7), sumatriptan 100 mg (n = 14), dexfenfluramine 15 mg (n=4), lorazepam 1.25 mg (n=4) and placebo (n=14). 311C90 10 mg and, to a lesser degree, 5 mg significantly increased the mean ASF slope (p=0.007 and 0.05 vs placebo). There was a significant positive correlation between plasma levels of 311C90 and ASF slope changes. Sumatriptan and lorazepam had little effect, but dexfenfluramine produced a significant ASF slope decrease. 311C90 is able to modify a CNS activity that is modulated by serotonin, i.e. the IDAP. This effect is probably the consequence of its superior lipophilicity compared to sumatriptan and of activation of prejunctional 5HT(1B/D) autoreceptors, which lowers central serotonin release and thus the preactivation level of sensory cortices.

Original languageEnglish
Pages (from-to)849-854
Number of pages6
JournalCephalalgia
Volume17
Issue number8
DOIs
Publication statusPublished - 1997

Fingerprint

zolmitriptan
Auditory Evoked Potentials
Serotonin
Central Nervous System
Biomarkers
Sumatriptan
Dexfenfluramine
Lorazepam
Placebos
Trigeminal Nuclei
Autoreceptors
Migraine Disorders

Keywords

  • 5HT(1B/D) receptors
  • Cortical auditory evoked potential
  • Migraine
  • Serotonin
  • Zolmitriptan

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

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title = "Intensity dependence of the cortical auditory evoked potentials as a surrogate marker of central nervous system serotonin transmission in man: Demonstration of a central effect for the 5HT(1B/1D) agonist zolmitriptan (311C90, Zomig{\circledR})",
abstract = "As shown in animal studies, 5HT(1B/D) agonists can inhibit activity in the trigeminal nucleus caudalis, which may be advantageous for their antimigraine effect. To demonstrate a possible central nervous system (CNS) action of these compounds in man we studied their effect on the intensity dependence of the cortical auditory evoked potentials (IDAPs), thought to be inversely related to central serotonergic transmission. An amplitude/stimulus intensity function (ASF) slope was computed in healthy volunteers and migraine patients between attacks before and 2 h after oral 311C90 (zolmitriptan 'Zomig') 10 mg (n=14), 311C90 5 mg (n=7), sumatriptan 100 mg (n = 14), dexfenfluramine 15 mg (n=4), lorazepam 1.25 mg (n=4) and placebo (n=14). 311C90 10 mg and, to a lesser degree, 5 mg significantly increased the mean ASF slope (p=0.007 and 0.05 vs placebo). There was a significant positive correlation between plasma levels of 311C90 and ASF slope changes. Sumatriptan and lorazepam had little effect, but dexfenfluramine produced a significant ASF slope decrease. 311C90 is able to modify a CNS activity that is modulated by serotonin, i.e. the IDAP. This effect is probably the consequence of its superior lipophilicity compared to sumatriptan and of activation of prejunctional 5HT(1B/D) autoreceptors, which lowers central serotonin release and thus the preactivation level of sensory cortices.",
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AU - Schoenen, J.

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