Systemic and regional hemodynamic effects of the putative 5-HT1A receptor agonist flesinoxan in the cat.
The systemic and regional hemodynamic effects of the centrally acting putative 5-HT1A receptor agonist flesinoxan (3, 10, 30, and 100 micrograms/kg) were investigated in the anesthetized cat and compared with those of 8-hydroxy-2(di-n-prophylamino) tetralin (8-OH-DPAT 3, 10, 30, and 100 micrograms/kg) and clonidine (0.3, 1, 3, and 10 micrograms/kg). Cardiac output (CO) was measured with a precalibrated electromagnetic flow probe placed on the ascending aorta, and regional blood flows and conductances were measured with radioactive microspheres. Flesinoxan and 8-OH-DPAT caused a decrease in blood pressure (BP 44 and 37%, respectively, at 100 micrograms/kg) mainly resulting from an increased peripheral vascular conductance; in the case of 8-OH-DPAT, however, a reduction in CO (34%) also contributed. Clonidine decreased BP (12% at 10 micrograms/kg) by reducing CO (31%). All three drugs decreased heart rate (HR). Flesinoxan and 8-OH-DPAT decreased tissue perfusion in the heart, lungs, gastrointestinal tract, eyes, and skin, but both renal and cerebral blood flows were preserved as a result of increased vascular conductances. These two drugs also redistributed intrarenal blood flow from the outer cortex toward the inner cortex and medulla. Low doses of clonidine tended to increase but higher doses decreased organ blood flows, especially to the heart, lungs, liver, and eyes. Clonidine did not redistribute intrarenal blood flows. These results establish that the 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT elicited a systemic and regional hemodynamic profile that differs from that of the alpha 2-adrenoceptor agonist clonidine.
Dreteler
G H
GH
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
Wouters
W
W
Saxena
P R
PR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000959:Antihypertensive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C056895:flesinoxan; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003000:Clonidine