title: Acute effect of KA-672, a putative cognitive enhancer, on neurotransmitter receptor binding in mouse brain.
abstract: 7-Methoxy-6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy]-3,4-dim ethyl-2H-1-benzopyran-2-one hydro-chloride (KA-672), structurally related to naturally occurring coumarins, has been described as a potential drug for enhancing cognitive functions. However, a detailed characterization of the pharmacological profile of KA-672 in vivo is still lacking. Quantitative neurotransmitter receptor autoradiography was used as a tool to screen for KA-672-induced changes in a number of transmitter receptors including cholinergic, noradrenergic, glutamatergic, GABAergic, and serotonergic subtypes throughout the brain. Two hours following treatment of mice with 1 mg/kg KA-672 per os, slight increases of nicotinic and M1-muscarinic cholinergic receptor binding, of alpha2-and beta-adrenoceptor as well as 5-HT1A receptors in various cerebral cortical regions were observed, whereas 5-HT2A binding sites were strikingly increased throughout the brain following KA-672 treatment. In contrast, (+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding was significantly decreased in some cortical regions after drug treatment. No effects of KA-672 treatment on N-methyl-D-aspartate, kainate, GABA(A) and benzodiazepine receptor as well as M2-muscarinic cholinergic and high-affinity choline uptake binding were observed. As interactions between the cholinergic, noradrenergic and serotonergic neurotransmission have been stressed to play important roles in realizing learning and memory events, the cognition-enhancing effects of KA-672 may be due to this complex in vivo pharmacological profile of KA-672.
authors.affiliation: Paul Flechsig Institute for Brain Research, Department of Neurochemistry, University of Leipzig, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Reisner
authors.forename: M
authors.initials: M
authors.lastname: Nöldner
authors.forename: S
authors.initials: S
authors.lastname: Rossner
authors.forename: S S
authors.initials: SS
authors.lastname: Chatterjee
authors.forename: V
authors.initials: V
authors.lastname: Bigl
authors.forename: R
authors.initials: R
authors.lastname: Schliebs
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010879:Piperazines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D044402:Receptor, Serotonin, 5-HT2A; D018091:Receptors, AMPA / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D014316:Tritium
chemical_list: D001578:Benzopyrans; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D018091:Receptors, AMPA; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D018079:Receptors, GABA; D018092:Kainic Acid Receptors; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D014316:Tritium; C112452:Ensaculin