These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Estimation of apparent pA2 values for WAY 100635 at 5-HT1A receptors regulating 5-hydroxytryptamine release in anaesthetised rats.
    Author: Assié MB, Koek W.
    Journal: Eur J Pharmacol; 2000 Dec 08; 409(2):173-7. PubMed ID: 11104831.
    Abstract:
    5-HT1A receptor agonists decrease 5-hydroxytryptamine (5-HT) terminal release by activating somatodendritic 5-HT1A autoreceptors. The selective 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (WAY 100635) inhibits these effects of 5-HT1A receptor agonists. The present study was aimed at estimating apparent pA2 values for WAY 100635 to antagonise 5-HT1A receptor agonist-induced decrease in 5-HT release in rat hippocampus. Extracellular concentrations of 5-HT were measured in microdialysis samples after administration of cumulative doses of 5-HT1A receptor agonists with different intrinsic activity, alone or in the presence of increasing doses of WAY 100635. Administration of cumulative doses of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.01-40 mg/kg), 1[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphtyl)pipe razine (S 14506) (0.00063-2.5 mg/kg), or buspirone (0.16-40 mg/kg), dose-dependently decreased the extracellular concentrations of 5-HT in the ventral hippocampus. Pre-treatment with WAY 100635 (0.01-0.63 mg/kg) shifted the dose-response curve of each agonist to the right in a dose-dependent manner. WAY 100635 antagonised the effects of all three compounds in a competitive manner, with an estimated apparent in vivo pA2 value of 7.95 (95% confidence limits: 7.66-8.24). Taken together, the results are evidence that buspirone, S 14506 and 8-OH-DPAT, administered in cumulative doses, decreased 5-HT release by activating similar 5-HT1A receptors, because a common apparent pA2 value was obtained for WAY 100635. The results also show that orderly microdialysis data can be obtained using cumulative dosing, which enables one to collect dose-response data rapidly, with fewer animals.
    [Abstract] [Full Text] [Related] [New Search]