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.

Article date: 1985/8/1

PubMed ID: 2991521

Journal name: Journal of medicinal chemistry (ISSN: 0022-2623)


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.

This document is available from: http://directlinks.cc/files/muscimol/2991521.pdf

Author List: Nordmann R, Graff P, Maurer R, Gähwiler B H

Publication Types: Comparative Study; Journal Article

Substances mentioned in the article: Anticonvulsants; Isoxazoles; Oxazoles; Receptors, GABA-A; Muscimol; 2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo(5,4-c)pyridine; gaboxadol;

Mesh terms: Animals; Anticonvulsants; Cerebellum/drug effects; Electrophysiology; Female; Isoxazoles/chemical synthesis; Male; Mice; Muscimol/metabolism; Oxazoles/pharmacology; Rats; Receptors, GABA-A/drug effects;

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