Cardiovascular actions of buflomedil and possible mechanisms involved.
Cardiovascular effects of buflomedil (Bufedil) were studied in dogs, rabbits and guinea pigs. 1. In pentobarbital-anesthetized dogs, buflomedil (0.32-5.12 mg/kg i.v.) induced a dose-dependent fall of blood pressure and a slight increase of heart rate at 0.32-1.28 mg/kg but a heart rate decrease at 2.56 and 5.12 mg/kg. 2. Buflomedil administered into the maxillary (10-320 micrograms/kg), internal carotid (40-320 micrograms/kg) and vertebral artery (20-640 micrograms/kg) increased respective blood flows dose-dependently. 3. Buflomedil (i.v.) also produced dose-dependent increases of the maxillary blood flow at 0.08-0.64 mg/kg, internal carotid flow at 1.28-5.12 mg/kg and vertebral flow at 0.32-5.12 mg/kg, respectively. These increasing effects were attenuated at larger doses because of marked hypotension. 4. Buflomedil (10 mg/kg i.v.) reduced pressor responses to norepinephrine (noradrenaline) and enhanced depressor responses to isoprenaline (isoproterenol), without affecting depressor responses to acetylcholine and positive chronotropic responses to norepinephrine and isoprenaline. 5. After buflomedil (i.v.), the femoral and coronary blood flow increased dose-dependently while renal blood flow decreased. These increasing effects were also reduced at larger doses because of hypotension. 6. Buflomedil (i.v.) induced a dose-dependent increase of cardiac output at 0.16-0.64 mg/kg, biphasic changes at 1.28 and 2.56 mg/kg and a marked decrease and subsequent slight increase at a large dose of 5.12 mg/kg. 7. 4-Desmethylbuflomedil (i.v.); elicited dose-dependent biphasic changes of blood pressure at 0.64-5.12 mg/kg, and a slight increase of heart rate at 0.32-2.56 mg/kg but decreases at 5.12 mg/kg. It also elevated, dose-dependently, the maxillary blood flow at 0.16-5.12 mg/kg and vertebral flow at 1.28-5.12 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
K
K
Kushiku
M
M
Ohba
T
T
Mikagi
S
S
Nuki
Y
Y
Araki
T
T
Furukawa
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013233:Stellate Ganglion / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D011759:Pyrrolidines; D014665:Vasodilator Agents; D007545:Isoproterenol; D000109:Acetylcholine; C010651:buflomedil; D009638:Norepinephrine