Antagonists of benzodiazepines: functional aspects.

Various effects of BZ tranquilizers can be attenuated or blocked by a number of non-specific antagonists. These drugs do not interact with specific BZ receptors, but affect various transmitter systems that are primarily or secondarily involved in the effects of benzodiazepines; of interest are agents that interact with GABA synthesis, GABA receptors and chloride channels, cholinergic mechanisms, with endogenous opioids and purines. Such non-specific antagonists are of potential usefulness in identifying neuronal systems that underly the various effects of BZ's. BZ receptor blockers interact with BZ's at their specific receptors. Two fundamentally different types of specific antagonists exist: competitive inhibitors with a negligible agonistic or inverse agonistic component, such as Ro 15-1788 and Ro 15-3505, and inverse agonists, e.g. beta-carboline derivatives which alter the BZ receptor in such a way that effects are produced which are the opposite of those induced by full agonists. The three classes of ligands of the BZ receptor, namely agonists, competitive antagonists and inverse agonists have greatly contributed to the current knowledge of the operation of BZ receptors.