Cardiovascular and side effects of flesinoxan in conscious hypertensive dogs. Modulation by prazosin.
Previous studies on anaesthetized animals indicate that flesinoxan exerts hypotensive effects via stimulation of central 5-HT1A receptors. The purpose of the present study was to investigate the cardiovascular and side effects of flesinoxan in conscious, renal hypertensive dogs at rest and during exercise. Animals were pretreated with prazosin (2.5 or 7.5 nmol/kg) to verify a reduction of dose-dependent side effects, as occurred in normotensive dogs. A decrease in blood pressure without reflex tachycardia was observed only with the lower dose of flesinoxan (0.1 mumol/kg). The higher dose (0.2 mumol/kg) led to an increase in blood pressure and heart rate. The increase in heart rate during exercise was diminished by 0.2 mumol/kg flesinoxan. Pretreatment with prazosin resulted in an additive hypotensive effect at rest. Side effects, occurring primarily after the higher dose of flesinoxan, were not influenced by prazosin. It is concluded that flesinoxan is not likely to be efficacious in antihypertensive therapy.
Huber
S
S
Department of Cardiovascular Pharmacology, Universität Wien, Vienna, Austria.
Grohs
J G
JG
Raberger
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006977:Hypertension, Renal / Q000503:physiopathology*; D009020:Morphine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D011224:Prazosin / Q000494:pharmacology* / Q000633:toxicity; D013565:Sympatholytics / Q000494:pharmacology
D000959:Antihypertensive Agents; D010879:Piperazines; D013565:Sympatholytics; C056895:flesinoxan; D009020:Morphine; D010424:Pentobarbital; D011224:Prazosin