CONTRACTILE EFFECTS OF 8-HYDROXY-2-(DI-N-PROPYLAMINO) TETRALIN AND FLESINOXAN IN HUMAN ISOLATED BASILAR ARTERY

The aim of the present study was to assess the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and flesinoxan in ring preparations of human basilar artery. 5-Hydroxytryptamine-(5-HT), 8-OH-DPAT and flesinoxan induced concentration-dependent contractions of human basilar artery, the rank order of agonist potency being 5-HT > 8-OH-DPAT almost-equal-to flesinoxan. The rank order of maximum response, relative to 5-HT was 5-HT (100%) >> 8-OH-DPAT (40.4 +/- 4.4%) >> flesinoxan (7.0 +/- 2.3%). The contractile effects of 8-OH-DPAT were blocked by phentolamine (10-mu-M) but not by labetalol (10-mu-M). Spiperone (1-mu-M) had no significant effect on either 5-HT or 8-OH-DPAT-induced contraction, however methiothepin (100 nM) produced inhibition of both 5-HT- and 8-OH-DPAT-induced contraction of human basilar artery. In addition, flesinoxan (100-mu-M) produced blockade of 5-HT-, 8-OH-DPAT- and sumatriptan (a 5-HT1-like receptor agonist)-induced contraction of human basilar artery, although full concentration-effect curves were not obtained. In some preparations 8-OH-DPAT produced a concentration-dependent relaxation of tone. This effect was particularly apparent in the presence of phentolamine. We conclude from the relative rank order of antagonist potency that 8-OH-DPAT and 5-HT produce contraction of the human basilar artery by activation of the same receptor, a 5-HT1-like receptor distinct from the 5-HT1A receptor subtype. Flesinoxan can also antagonise the effects of activation of 5-HT1-like receptors to a number of 5-HT receptor agonists.