title: Synthesis and biological evaluation of GABA derivatives able to cross the blood-brain barrier in rats.
abstract: 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.
authors.affiliation: Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, Piazzale A. Moro 5, 00185 Rome, Italy. vincenzo.carelli@uniroma1.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carelli
authors.forename: Felice
authors.initials: F
authors.lastname: Liberatore
authors.forename: Luigi
authors.initials: L
authors.lastname: Scipione
authors.forename: Gianfabio
authors.initials: G
authors.lastname: Giorgioni
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.forename: Mariannina
authors.initials: M
authors.lastname: Impicciatore
authors.forename: Vigilio
authors.initials: V
authors.lastname: Ballabeni
authors.forename: Francesco
authors.initials: F
authors.lastname: Calcina
authors.forename: Francesca
authors.initials: F
authors.lastname: Magnanini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D001711:Biotransformation; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006868:Hydrolysis; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D009682:Magnetic Resonance Spectroscopy; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010084:Oxidation-Reduction; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D006993:Hypnotics and Sedatives; D018727:Muscarinic Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D010424:Pentobarbital