Interaction of carbolines and some GABA receptor ligands with the GABA and the benzodiazepine receptors.

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.