Synthesis and biological evaluation of GABA derivatives able to cross the blood–Brain barrier in rats

Autor:	Elisabetta Barocelli, Francesca Magnanini, Mariannina Impicciatore, Francesco Calcina, Felice Liberatore, Vincenzo Carelli, Luigi Scipione, Vigilio Ballabeni, Gianfabio Giorgioni, Antonio Di Stefano
Rok vydání:	2003
Předmět:	Atropine Magnetic Resonance Spectroscopy medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide Muscarinic Antagonists Oxidative phosphorylation Pharmacology Blood–brain barrier Binding Competitive Biochemistry Chemical synthesis Hypnotic In vivo Drug Discovery medicine Animals Hypnotics and Sedatives Rats Wistar Pentobarbital Molecular Biology Biotransformation gamma-Aminobutyric Acid Injections Intraventricular Dose-Response Relationship Drug Chemistry Hydrolysis Organic Chemistry Biological activity Receptors GABA-A In vitro Rats medicine.anatomical_structure Receptors GABA-B Blood-Brain Barrier Injections Intravenous Molecular Medicine Female Sleep Oxidation-Reduction Injections Intraperitoneal
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 13:3765-3769
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2003.07.004
Popis:	Two new GABA derivatives, 1 and 2, were synthesized and tested for their capacity to display CNS activity, which was assessed by determining the effects on the duration of pentobarbital-induced hypnosis in rats. Compound 1, peripherally injected, significantly prolonged the hypnosis time, a typical GABA-mimetic effect, while both intracerebroventricular and intravenous administration of compound 2 surprisingly shortened the hypnotic effect in an atropine-sensitive way. The study was extended also to compounds 1a, 1b and 2a, putative oxidative/hydrolytic metabolites of 1 and 2.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db82c8b9e7cb71bf43cbb9db1c93e239 https://doi.org/10.1016/j.bmcl.2003.07.004 Zobrazit plný text záznamu Full Text from ScienceDirect