title: Central 5-HT1A receptors and the mechanism of the central hypotensive effect of (+)8-OH-DPAT, DP-5-CT, R28935, and urapidil.
abstract: This study investigated the central hypotensive effects of drugs that possess a high affinity for central 5-hydroxytryptamine (5-HT1A) binding sites; (+)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), N,N-dipropylcarboxamidotryptamine (DP-5-CT), erythro-1-(1-[2(1,4-benzodioxan-2-yl)-2-hydroxyethyl]- 4-piperidyl)-2-benzimidazolinone (R28935) and urapidil proved to possess high affinity and selectivity for central 5-HT1A binding sites, labeled by [3H]8-OH-DPAT. (+)8-OH-DPAT (0.1-10 micrograms/kg) given through the left vertebral artery of chloralose-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 micrograms/kg (+)8-OH-DPAT, 3 micrograms/kg DP-5 CT, and 3 micrograms/kg R28935 could be blocked by 100 micrograms/kg (-)pindolol, indicating that central 5-HT1A receptors are involved. High doses of (+)8-OH-DPAT (3-10 micrograms/kg) can also lower blood pressure by activating central alpha 2-adrenoceptors. The hypotensive effect of 300 micrograms/kg urapidil given through the vertebral artery could not be blocked by (-)pindolol. These results indicate the involvement of central 5-HT1A receptors in the mechanism of the central hypotensive activity of (+)8-OH-DPAT, DP-5-CT, and R28935.
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002415:Cats; D004146:Dioxanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D005260:Female; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects*; D013552:Swine; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D004146:Dioxanes; D004147:Dioxins; D009281:Naphthalenes; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; C010402:R 28935; C055895:N,N-dipropylcarboxamidotryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015568:urapidil