title: Interaction of carbolines and some GABA receptor ligands with the GABA and the benzodiazepine receptors.
abstract: The binding of different drugs were investigated on benzodiazepines and GABA receptors using P2 fraction or 0.05% Triton X-100 treated membrane preparation (TX-100 P) obtained from rat's CNS. Bicuculline and picrotoxin have the ability to modulate the specific 3H-flunitrazepam binding to its receptor present in P2 fraction; this modulation decreases for bicuculline and disappears for picrotoxin when a TX-100 P was used. Bicuculline at the opposite of picrotoxin displaces 3H-GABA binding on TX-100 P. The beta-CCE binds to the brain benzodiazepines receptor with a high affinity (IC50 = 8.5 nM on TX-100 P) and does not inhibit the binding of 3H-GABA on TX-100 P. On the contrary, other related carbolines such as harmine, harmaline, harmane and harmalol have a much lower ability to inhibit flunitrazepam binding (IC50 between 28 and 130 microM with TX-100 P) and can also inhibit 3H-GABA binding (IC50 between 75 and 186 microM with TX-100 P). But the inhibition of 3H-GABA binding by those related carbolines can't be reversed by a benzodiazepine like flunitrazepam or a benzodiazepine antagonist like Ro 15-1788.
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002243:Carbolines / Q000494:pharmacology*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D006246:Harmaline / Q000494:pharmacology; D006247:Harmine / Q000494:pharmacology; D066298:In Vitro Techniques; D017830:Octoxynol; D010852:Picrotoxin / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D001640:Bicuculline; D002243:Carbolines; D005445:Flunitrazepam; D006246:Harmaline; D006247:Harmine; D017830:Octoxynol; D010852:Picrotoxin; D011092:Polyethylene Glycols; D011963:Receptors, GABA-A