Benzodiazepine inhibition of flunitrazepam receptor binding, adenosine uptake, and pentylenetetrazol-induced seizures in mice.

The potencies of seven benzodiazepines (BDZs) were established by three tests: inhibition of [3H]flunitrazepam receptor binding, inhibition of [3H]adenosine uptake, and prevention of pentylenetetrazol-induced seizures in mice. There is a high correlation between the potency for inhibition of [3H]flunitrazepam receptor binding and the antipentylenetetrazol potencies of benzodiazepines (r = 0.941; p less than 0.01). The antipentylenetetrazol potencies of benzodiazepines correlate well with their ability to inhibit [3H]adenosine uptake (r = 0.860; p less than 0.05 and greater than 0.01). However, there is no significant correlation between the potency for the inhibition of [3H]flunitrazepam receptor binding and the potency for inhibition of [3H]adenosine uptake (r = 0.751; p greater than 0.05). In addition, there is a marked difference in BDZ potency as measured by these two tests in vitro. The ratios of the Ki values (Ki2/Ki1) range from 98 for BDZ I to 64615 for clonazepam. The data presented indicate that antipentylenetetrazol activity of benzodiazepines results from an interaction between BDZ and nanomolar affinity BDZ receptors.