Interaction of a water-soluble derivative of delta-9-tetrahydrocannabinol with [3H]diazepam and [3H]flunitrazepam binding to rat brain membranes.

We have tested the effect of a psychoactive water-soluble derivative of delta-9-tetrahydrocannabinol, SP-111A, on the binding of [3H]diazepam and [3H]flunitrazepam to rat brain membranes. It was found that SP-111A reduced the specific binding of [3H]diazepam and [3H]flunitrazepam. The inhibition by SP-111A was dependent not only on the concentration of the ligand but also on the protein content of membrane preparations. The inhibition of the specific binding of [3H]diazepam by SP-111A was found to be competitive with Ki value of 3.1 microM. In the presence of 7.5 microM SP111A the apparent Kd of [3H]diazepam binding increased from 4.3 nM to 12.5 nM, without affecting the Bmax. The inhibition of the specific binding of [3H]flunitrazepam by SP-111A was also competitive, however, the IC50 was higher than with [3H]diazepam. The inhibition by SP-111A appeared to be caused by its tight binding to the benzodiazepine binding sites of brain membranes.