title: Synthesis and pharmacological evaluation of cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine: a structural analogue of the GABA agonist THIP.
abstract: The pharmacological activities of the GABA agonist muscimol (1) and its dihydro analogue (2) have been shown to be almost identical. The closely related 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, 3), although biologically less active than muscimol, was selected for clinical trials. We report the synthesis of the so far elusive cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine (cis-DH-THIP, cis-4), which--surprisingly--is devoid of any GABAergic activity.
authors.forename: R
authors.initials: R
authors.lastname: Nordmann
authors.forename: P
authors.initials: P
authors.lastname: Graff
authors.forename: R
authors.initials: R
authors.lastname: Maurer
authors.forename: B H
authors.initials: BH
authors.lastname: Gähwiler
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D010080:Oxazoles; D011963:Receptors, GABA-A; D009118:Muscimol; C045969:2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo(5,4-c)pyridine; C015542:gaboxadol