Central 5-HT(1A) receptors and the mechanism of the central hypotensive effect of (+)8-OH-DPAT, DP-5-CT, R28935, and urapidil

Doods, H. N., Boddeke, H. W. G. M., Kalkman, H. O., Hoyer, D., Mathy, M-J. & Van Zwieten, P. A., 12-Nov-1988, In : Journal of Cardiovascular Pharmacology. 11, 4, p. 432-437 6 p.

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This study investigated the central hypotensive effects of drugs that possess a high affinity for central 5-hydroxytryptamine (5-HT(1A)) binding sites; (+)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), N,N-dipropylcaboxamidotryptamine (DP-5-CT), erythro-1-{1-[2(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-4-piperidyl}- -benzimidazolinone (R28935) and urapidil proved to possess high affinity and selectivity for central 5-HT(1A) binding sites, labeled by [3H]8-OH-DPAT. (+)8-OHDPAT (0.1-10 μg/kg) given through the left vertebral artery of choralose-anesthetized cats, lowered blood pressure by a biphasic dose-response curve. When given systemically, 10- to 100-fold higher doses of (+)8-OH-DPAT were necessary to obtain the same hypotensive effect when compared with central administration. Besides 8-OH-DPAT, R28935, DP-5-CT and urapidil also lowered blood pressure by a central mechanism in doses that were ineffective when given systemically. The central hypotensive effect of 0.3 μg/kg (+)8-OH-DPAT, 3 μg/kg DP-5 CT, and 3 μg/kg R28935 could be blocked by 100 μg/klg (-)pindolol, indicating that central 5-HT(1A) receptors are involved. High doses of (+)8-OH-DPAT (3-10 μg/kg) can also lower blood pressure by activating central α2-adrenoceptors. The hypotensive effect of 300 μg/kg urapidil given through the vertebral artery could not be blocked by (-)pindolol. These results indicate the involvement of central 5-HT(1A) receptors in the mechanism of the central hypotensive activity of (+)8-OH-DPAT, DP-5-CT, and R28935.
Original languageEnglish
Pages (from-to)432-437
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Issue number4
Publication statusPublished - 12-Nov-1988


  • idazoxan, pindolol, serotonin receptor, urapidil, animal experiment, cat, central nervous system, diagnosis, nonhuman

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