Inhibition of R 28935- and R 29814-induced hypotension by prazosin in anaesthetized normotensive rats.
|
| Abstract |
The intravenous administration of erythro 1-(1-[2-(1,4-benzodioxane-2-yl)-2-hydroxyethyl]-4-piperidyl)-2-benzimidazolinone R 28935) and the threo from R 29814 to anaesthetized normotensive rats showed a dose-dependent decrease in mean arterial pressure. Previous (-1 hr) intraperitoneal (0.1 mg/kg) as well as subcutaneous (0.03 mg/kg) treatment with the alpha 1-adrenoceptor blocking drug prazosin antagonized the hypotensive responses to R 28935 and R 29814. The selective antagonist of alpha 2-adrenoceptors yohimbine (0.5 mg/kg) was ineffective. On the other hand, the hypotensive action of clonidine was hardly affected by this prazosin treatment, whereas yohimbine now significantly impaired it. R 28935 and R 29814 showed no direct alpha-adrenoceptor stimulating properties and were moderately active in inhibiting the pressor response to (-)-phenylephrine in pithed normotensive rats when compared with phentolamine and prazosin. The results confirm and extend previous findings in cats. It is concluded that in some way central alpha 1-adrenoceptors are involved in the hypotensive mechanism of R 28935 (R 28914). However, central alpha 1-adrenoceptors are probably not the common sites of interaction, since any alpha 1-adrenoceptor-stimulating potency is lacking for R 28935 (R 29814) and their (moderate) affinity for alpha 1-adrenoceptors bears no relationship to their hypotensive activity.
|
|---|---|
| Authors | P B Timmermans, F P Slothorst-Grisdijk, H Y Kwa, P A van Zwieten |
| Journal | Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) Vol. 255 Issue 2 Pg. 309-20 (Feb 1982) ISSN: 0003-9780 [Print] Belgium |
| PMID | 7073408 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!