title: Phosphorus analogues of gamma-aminobutyric acid, a new class of anticonvulsants.
abstract: A series of phosphorus compounds, designed as analogues of gamma-aminobutyric acid (GABA) in that they possess a P = O moiety separated by three atoms from an amino or acetamido group, was synthesized and tested by using in vitro GABAA and GABAB receptor binding, GABA uptake assays, and was examined for anticonvulsant activity. Weak GABAB receptor affinity was noted for one agent, whereas six compounds displayed moderate to high potencies as inhibitors of electroshock- and pentylenetetrazol-induced seizures. The best anticonvulsant effect was found with the (m-aminophenyl) phosphinic acid compounds, with members of this class selected for further study.
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D001681:Biological Assay; D001921:Brain / Q000378:metabolism; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A; D012640:Seizures / Q000188:drug therapy; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D007202:Indicators and Reagents; D009943:Organophosphorus Compounds; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid