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Biochemical profile of anseculin (KA‐672) at different brain receptors
Author(s) -
Knauber J.,
Müller W.E.
Publication year - 2002
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10053
Subject(s) - prazosin , receptor , agonist , chemistry , endocrinology , ex vivo , pharmacology , potency , medicine , in vivo , antagonist , muscarinic acetylcholine receptor , cholinergic , rauwolscine , biology , in vitro , biochemistry , microbiology and biotechnology
Anseculin (KA‐672) is a multifunctional antidementia agent under development that may be of therapeutic value in the treatment of progressive neuronal and cognitive decline, which are common in Alzheimer disease. In vitro and ex vivo experiments have characterized anseculin as a potent functional antagonist of central α 1 ‐adrenoceptors. In comparison to prazosin, the in vitro potency of anseculin for α 1 ‐adrenoceptors is about 8 times less. Like prazosin, anseculin shows an inhibition of phenylephrine‐ (norepinephrine‐) induced accumulation of inositol phosphates. Oral treatment with 1 mg/kg anseculin or 1 mg/kg prazosin show similar effects on α 1 ‐adrenergic receptor binding ex vivo, indicating a greater ex vivo potency of anseculin on central α 1 ‐adrenergic receptors. Anseculin has only weak affinity for central muscarinic cholinergic receptors. Anseculin inhibited adenylate cyclase and reduced intracelluar cAMP levels of about 30%, similar to the 5‐HT 1A agonist, 8‐OH‐DPAT. Together with its high affinity for 5‐HT 1A receptors (IC 50 for 3 H‐8‐OH‐DPAT binding is about 8 nM), these data suggest that anseculin also exhibits 5‐HT 1A agonistic properties. Drug Dev. Res. 55:187–196, 2002. © 2002 Wiley‐Liss, Inc.