![]() Many of the Z-drugs are subtype selective (see subtypes discussed above) and are therefore novel in that they can provide specific effects (e.g., hypnotics with no anxiolytic effects).Ī review of the literature regarding hypnotics, including the nonbenzodiazepine Z-drugs, concluded that these drugs cause an unjustifiable risk to the individual and to public health and lack evidence of long-term effectiveness due to tolerance. Like the benzodiazepines, they exert their effects by binding to and activating the benzodiazepine site of the receptor complex. The nonbenzodiazepines are activators of the GABA-A receptor. Z-drugs differ from benzodiazepines in their chemical structure, which makes them unrelated molecularly to benzodiazepines. For this reason, the Z-drugs have similar effects and also risks to the benzodiazepines. The pharmacodynamics (biochemical and physiological effects) of Z-drugs are almost identical to the benzodiazepine drugs. For this reason, they have very short half-lives ranging from 2-6 hours (in the non-elderly). Most Z-drugs, like Zolpidem ( Ambien), zaleplon (Sonata) and eszopiclone ( Lunesta), are approved and prescribed for insomnia or sleep disorders. Non-benzodiazepines, sometimes referred to as ‘Z-drugs’ or hypnotics, are also a class of psychoactive drugs that are very similar to the benzodiazepines. What are Z Drugs and How Are They Similar to Benzodiazepines? All benzodiazepines combine, to a greater or lesser extent, with all these subtypes and all enhance GABA activity in the brain. The alpha 1 subtype is responsible for sedative effects, the alpha 2 for anti-anxiety effects, and both alpha 1 and alpha 2 (as well as alpha 5) for anticonvulsant effects. There are also various subtypes of benzodiazepine receptors, all of which have slightly different actions. These direct and indirect actions are responsible for the well-known adverse effects of dosage with benzodiazepines. Other benzodiazepine receptors not linked to GABA are present in the kidney, colon, blood cells and adrenal cortex and these may also be affected by some benzodiazepines. When the brain’s output of excitatory neurons is reduced, a consequence of the enhancement of GABA’s inhibitory activity caused by benzodiazepines, there may be impairment of certain functions, as the excitatory neurotransmitters are necessary for normal alertness, memory, muscle tone and coordination, emotional responses, endocrine gland secretions, heart rate and blood pressure control and a host of other functions. In depth information on how the GABA-A receptors work with benzodiazepines can be found here. FDA information for Ativan states withdrawal symptoms can be experienced by some after as little as one week of use, suggesting uncoupling occurs even with shorter-term use. This may be due to changes in GABA-A receptor gene expression where the neurons swap out GABA-A receptors that contain subunits benzos bind to with ones that don’t, to combat the action of the drug. Uncoupling results in a decrease in the ability of BZs to potentiate the action of GABA on GABA-A receptors and in a decrease in the ability of GABA to potentiate BZ binding. Long-term benzo usage can cause what is known as ‘uncoupling’ of the GABA-A receptor. This short video explains this concept visually: Combination of a benzodiazepine at this site acts as a booster to the actions of GABA, allowing more chloride ions to enter the neuron, making it even more resistant to excitation. Benzodiazepines also bind to their own receptors (benzodiazepine receptors) that are situated on the GABA-A receptor. ![]() These negative chloride ions make the neuron less responsive to other neurotransmitters (norepinephrine, serotonin, acetylcholine and dopamine) which would normally excite it. Once GABA is bound to the GABA-A receptor, the neuron opens a channel which allows chloride ions to pass inside of the neuron. Simply put, GABA sends its inhibitory message by binding at special sites called GABA-A receptors on the outside of the receiving neuron. When the “car” takes off speeding down the road (excitability of the nervous system), GABA functions as the “brakes” to calm and slow it down. If your nervous system was a car, GABA functions much like the “brakes”. Its role is in reducing neuronal excitability and, in humans, it is also responsible for the regulation of muscle tone. GABA is the chief inhibitory neurotransmitter in the mammalian central nervous system.
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