Pharmacologic properties of a novel Ca2+ entry blocker, AJ-2615, in vitro
| Autor: | Mikio Kurokawa, Takashi Nukuda, Buichi Fujitani, Teruaki Une, Kiyoshi Furukawa, Hirofumi Okamura, Masanobu Komiya |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Agonist
Dibenzothiepins Male medicine.medical_specialty Calmodulin medicine.drug_class Muscle Relaxation Aorta Thoracic In Vitro Techniques Muscle Smooth Vascular Piperazines Dogs Nifedipine Internal medicine medicine.artery medicine Prazosin Animals Diltiazem Rats Wistar Pharmacology Aorta Binding Sites biology Chemistry Biological activity 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester Receptors Adrenergic alpha Calcium Channel Blockers Rats Endocrinology biology.protein Potassium Verapamil Calcium Rabbits Cardiology and Cardiovascular Medicine medicine.drug Muscle Contraction |
| Zdroj: | Journal of cardiovascular pharmacology. 22(6) |
| ISSN: | 0160-2446 |
| Popis: | We studied the in vitro vascular relaxant properties of AJ-2615, (+/-)-N-[6,11-dihydrodibenzo[b,e]-thiepin-11-yl]-4-[4- fluorophenyl]-1-piperazinebutanamide monomaleate, a novel compound with long-lasting antihypertensive activity. AJ-2615 inhibited the high K(+)-induced contractile response in rat aorta with an IC50 of 2.08 x 10(-8) M. It was 13 times less potent than nifedipine and 3, 10, and 15 times more potent than verapamil, diltiazem, and fluanarizine, respectively. AJ-2615 also inhibited the high K(+)-induced 45Ca influx in rat aorta at almost the same concentration as that for inhibition of the contractile response. The inhibition of 45Ca influx was reversed by Bay k 8644, a Ca2+ channel agonist. The effects of AJ-2615 on the contractile response and Ca2+ influx persisted for at least 120 min after AJ-2615 was removed from the medium. These results indicate that AJ-2615 acts directly on the potential-dependent Ca2+ channel in a long-lasting manner. AJ-2615 inhibited [3H]prazosin binding to dog aortic membranes (IC50 = 1.25 x 10(-8) M) and phenylephrine-induced contractile response in superior mesenteric artery (SMA) of rabbits (IC50 = 3.87 x 10(-8) M), indicating that AJ-2615 has potent alpha 1-adrenoceptor blocking activity. AJ-2615 at 10(-6) M did not inhibit the caffeine-induced contractile response in rabbit SMA in Ca(2+)-free medium, nor did it inhibit calmodulin (CAM) activity.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|