Evidence that SL75102 is an agonist at GABAb as well as GABAa receptors.
The compound SL75102 ([alpha(4-chlorophenyl)5-fluoro 2-hydroxy benzilidene-amino]-4-butanoate sodium) is a GABA-mimetic at bicuculline-sensitive and -insensitive receptors. It depolarized rat isolated superior cervical ganglia in a dose-dependent manner (relative potency = 0.101 +/- 0.013; GABA = 1). Bicuculline methobromide (13 microM) antagonized this action of SL75102 and shifted the log dose-response curve to the same extent as the GABA curve. The evoked release of [3H]noradrenaline from rat isolated atria was also reduced by SL75102 in a GABA-like manner. SL75102 also displaced [3H]GABA and [3H]baclofen specifically bound to divalent cation dependent GABAB sites on rat synaptic membranes (relative potency approximately 0.1 GABA throughout). The butyramide from which SL75102 can be formed within the body (SL76002) was much less active at GABAB sites (less than 0.02 atria, 0.001 binding, GABA = 1). It is suggested that in addition to any direct action of SL76002 itself the products of SL76002 metabolism, SL75102 and GABA may exert effects via baclofen-sensitive GABAB as well as GABAA sites in mammalian brain.
D000200:Action Potentials; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D018756:GABA Antagonists; D005728:Ganglia, Sympathetic / Q000378:metabolism / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000927:Anticonvulsants; D018756:GABA Antagonists; D011941:Receptors, Adrenergic; D005680:gamma-Aminobutyric Acid; C017984:progabide acid