Biomaterial Database

[Sertindole, a novel alpha 1A-adrenoceptor selective antagonist]. 1997

Y Y Zhang, and Z Z Lu, and H Wei, and Q D Han

Institute of Vascular Medicine, Third Hospital, Beijing Medical University, Beijing 100083.

The antagonism effect of sertindole on alpha 1-AR subtypes was studied by combining radiologand binding assays in three cloned alpha 1-AR subtypes stably expressed in human embryonic kidney 293 cells and contractile response experiment in isolated rat blood vessels. The results showed that the affinity for sertindole in the cloned alpha 1A-AR (pKI 8.90 +/- 0.17) was 69-fold (pKI 7.06 +/- 0.09) and 132-fold (pKI 6.78 +/- 0.07) higher than that for the cloned alpha 1B- and alpha 1D-AR, respectively. The pA2 values for sertindole in antagonizing NE-induced vasoconstriction in isolated rat aorta and renal artery were shown to fit well to the pKI values on cloned alpha 1D- and alpha 1A-AR, respectively. Pretreatment of membrane preparations with sertindole for 30 min significantly reduced the maximal binding capacities. (Bmax) of 125 IBE2254 to the three cloned alpha 1-AR subtypes without alteration of affinities (KD values). In the presence of sertindole, the Bmax of 125IBE2254 binding to the cloned alpha 1-ARs were not significantly changed, while the KD values were significantly increased. Thus, sertindole is a selective irreversible competitive alpha 1-AR antagonist with alpha 1A subtype.

UI	MeSH Term	Description	Entries
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).
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D012077	Renal Artery	A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters.	Arteries, Renal,Artery, Renal,Renal Arteries
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004622	Embryo, Mammalian	The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.	Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia