Pharmacological profile of ME3221, a novel angiotensin II receptor antagonist
| Autor: | Fukio Konno, Mitsugu Hachisu, Mikio Yamamoto, Hiroko Ogino, Kazuyuki Fujishima, Kiyoaki Katano, Chen Hui, Ken-ichi Kawano, Sumie Yasuda, Jun Nagura |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Hypertension Renal medicine.drug_class Tetrazoles Aorta Thoracic Blood Pressure Angiotensin II receptor antagonist Pharmacology Bradykinin Essential hypertension Losartan Rats Sprague-Dawley Angiotensin Receptor Antagonists Species Specificity Heart Rate Rats Inbred SHR Internal medicine Renin–angiotensin system medicine Animals Antihypertensive drug Antihypertensive Agents Angiotensin II receptor type 1 Chemistry Angiotensin II Biphenyl Compounds Imidazoles Antagonist Callithrix medicine.disease Rats Femoral Artery Disease Models Animal Endocrinology Drug Evaluation Female Rabbits circulatory and respiratory physiology medicine.drug |
| Zdroj: | European Journal of Pharmacology. 274:201-211 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(94)00740-x |
| Popis: | The pharmacological profile of a new surmountable angiotensin AT1 receptor antagonist, ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, was studied in several animal models, and was compared with that of losartan. EF2831, 3-hydroxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, a metabolite of ME3221, is also a surmountable angiotensin AT1 receptor antagonist, whose potency was 1/30 that of ME3221 in vitro, but equal to or 1/3 of that of ME3221 in in vivo experiments. In rats and marmosets, ME3221 antagonized angiotensin II-induced pressor responses, but did not affect bradykinin-induced depressor responses. ME3221 lowered the blood pressure in renal hypertensive rats and spontaneously hypertensive rats (SHR), and its ED25 value was 3 times that of losartan. Repeated administration of ME3221 to SHR had a stable and long-lasting antihypertensive effect without influencing heart rate. Thus ME3221, like losartan, may be useful in the treatment of renal and essential hypertension. |
| Databáze: | OpenAIRE |
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