Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain.
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Johnson DE, Rollema H, Schmidt AW, McHarg AD
Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain.
Eur J Pharmacol. 2001 Aug 17;425(3):203-10.
- PubMed ID
- 11513839 [ View in PubMed]
- Abstract
In vivo microdialysis was used to assess the central serotonergic effects and extracellular brain levels of the 5-HT(1B/1D) receptor agonists eletriptan, zolmitriptan and sumatriptan in rats after intravenous and intracerebral administration, while their binding affinities and functional potencies were determined at 5-HT(1B), 5-HT(1D) and 5-HT(1A) receptors. In vitro studies showed that all three triptans are high affinity, full agonists at 5-HT(1B/1D) receptors, but that sumatriptan is functionally less potent as a 5-HT(1B/1D) agonist than zolmitriptan and eletriptan. Local intracortical perfusion with the compounds via the dialysis probe decreased cortical 5-HT (5-hydroxytryptamine, serotonin) release with ED(50) values of approximately 0.1 microM for eletriptan and zolmitriptan and 0.5 microM for sumatriptan. At 3.2 mg/kg i.v., both eletriptan and zolmitriptan decreased 5-HT levels by about 35%, while sumatriptan had no effect, despite the fact that maximal sumatriptan concentrations in cortical dialysates were higher (8.8 nM at 20 min) than those of zolmitriptan (5.9 nM at 20 min) and eletriptan (2.6 nM at 40 min). The observation that eletriptan and zolmitriptan produce almost identical central serotonergic effects, after intracerebral as well as after systemic administration, is in agreement with their comparable functional 5-HT(1B/1D) receptor agonist potencies and their free levels in cortical dialysates after 3.2 mg/kg i.v. On the other hand, the lack of central serotonergic effects of 3.2 mg/kg i.v. sumatriptan is likely due to its weaker functional 5-HT(1B/1D) receptor agonist potency than eletriptan and zolmitriptan, rather than lower brain levels, consistent with sumatriptan's fivefold lower potency after intracerebral administration.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Eletriptan 5-hydroxytryptamine receptor 1A Protein Humans UnknownAgonistDetails Eletriptan 5-hydroxytryptamine receptor 1B Protein Humans YesAgonistDetails Eletriptan 5-hydroxytryptamine receptor 1D Protein Humans YesAgonistDetails Sumatriptan 5-hydroxytryptamine receptor 1A Protein Humans YesAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1A Protein Humans NoAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1B Protein Humans YesAgonistDetails Zolmitriptan 5-hydroxytryptamine receptor 1D Protein Humans YesAgonistDetails