Diazepam and lorazepam

Generic (proprietary) Names: diazepam (Valium, Diastat) Manufacturer: Roche Laboratories (Valium), 340 Kingsland Street, Nutley, NJ 07110-1199 Generic (proprietary) Names: lorazepam (Ativan, Temesta) Manufacturer: Baxter Healthcare Corporation, Deerfield, IL 60015 Class: benzodiazepines (BNZs) Chemical Structure: diazepam, see Figure 90.1; lorazepam, see Figure 90.2 Mode of activity Major and minor sites of action: GABAA receptors in the brain and spinal cord. Receptor interactions: benzodiazepines enhance the actions of the neurotransmitter gamma-aminobutyric acid (GABA) on its receptor by modulating the GABA system in the brain, through the presence of high-affinity binding receptors. Interaction of benzodiazepines with GABAA receptors opens chloride ion channels, and enhances the frequency of chloride channel opening. It has been shown that in order to elicit the different effect, a different degree of GABAA receptor occupation is necessary. For instance, full agonists are able to elicit an anxiolytic or anticonvulsant effect at a low overall receptor occupation. Partial agonists, because of their lower intrinsic efficacy for enhancement of GABAergic transmission, need a higher receptor occupation to produce the same effect. However, the weak enhancement of GABAergic transmission by a partial agonist is not sufficient to induce sedative/hypnotic and muscle relaxant actions, since even full agonists need a rather high receptor occupation in order to produce these effects. As an example, the benzodiazepine agonistic receptor occupancy was found to differ among the various physiological responses in the following order: antipanic > anticonvulsion > sedation > muscle relaxation.