[Effects of M6434, an orally active alpha 1-adrenoceptor agonist, on experimental postural hypotension in rabbits and dogs]. 1992

T Dabasaki, and K Kobayashi, and Y Kato, and A Uemura
Fuji Central Research Laboratories, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.

We examined the effects of M6434 on mean blood pressure and heart rate in conscious rabbits and dogs and on experimental models of postural hypotension in conscious rabbits and anesthetized dogs. M6434, given orally, elevated the mean blood pressure in conscious rabbits and dogs. The pressor effect of M6434 was more potent than that of midodrine, but the bradycardiac action of M6434 was weaker than that of midodrine. M6434 (1.0 and 3.0 mg/kg, p.o.) prevented the head-up tilt-induced reductions of mean blood pressure and cerebral tissue blood flow in conscious rabbits, and these effects of M6434 were about 3 times more potent than those of midodrine. In the postural hypotension of anesthetized dogs, M6434 at the doses more than 10 micrograms/kg, i.v. also produced the preventive effects on mean blood pressure and cerebral tissue blood flow. These effects of M6434 were about 10-30 times more potent than those of midodrine. These results show that M6434 possesses a potent hypertensive effect with a weaker bradycardiac action and suggest that M6434 may be a potential candidate for an anti-hypotensive agent that can prevent the deterioration of hemodynamics in postural hypotension.

UI MeSH Term Description Entries
D007024 Hypotension, Orthostatic A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE. Hypotension, Postural,Orthostatic Hypotension,Postural Hypotension
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse

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