Acute effect of KA-872, a putative cognitive enhancer, on neurotransmitterreceptor binding in mouse brain

7-Methoxy-6-(3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy)3,4-dimethyl-2H-1 -benzopyran-2-one hydro-chloride (KA-672), structurally related to naturall y occurring coumarins, has been described as a potential drug for enhancing cognitive functions. However, a detailed characterization of the pharmacol ogical profile of KA-672 in vivo is still lacking. Quantitative neurotransm itter receptor autoradiography was used as a tool to screen for KA-672-indu ced changes in a number of transmitter receptors including cholinergic, nor adrenergic, 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 M-1-muscarinic cholinergic receptor bin ding, of alpha 2-and beta-adrenoceptor as well as 5-HT1A receptors in vario us cerebral cortical regions were observed, whereas 5-HT2A binding sites we re strikingly increased throughout the brain following KA-672 treatment. In contrast, (+/-)-alpha amino-3-hydroxy-5-methylisoxazole-4-propionic acid r eceptor binding was significantly decreased in some cortical regions after drug treatment. No effects of KA-672 treatment on N-methyl-D-aspartate, kai nate, GABA(A) and benzodiazepine receptor as well as M2-muscarinic choliner gic 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 compl ex in vivo pharmacological profile of KA-672. (C) 1999 Elsevier Science Ire land Ltd. All rights reserved.