Benzodiazepine centrally-mediating effects

Tenn, C. C. Niles, L. P. (1995). Central-type benzodiazepine receptors mediate the antidopaminergic effect of clonazepam and melatonin in 6-hydroxydopamine lesioned rats involvement of a GABAergic mechanism. J. Pharmacol. Exp. Ther. 274, 84-9. 

Benzodiazepines exert central depressant effects on spinal reflexes, in part mediated by the brainstem reticular system.3 For example, chlordiazepoxide depresses the duration of electrical after-discharge in the limbic system. Most benzodiazepines elevate the seizure threshold and therefore may be used as anticonvulsant medications. Diazepam, clonazepam, and clorazepate may be prescribed for this therapeutic purpose. 

The benzodiazepines are a group of chemically related drugs, the best-known members of which are chlordiazepoxide (Librium ) and diazepam (Valium ). There are many others with variations in properties, particularly onset of effects and duration of action. The most recognized effects of the benzodiazepines are centrally mediated and include sedation, hypnosis, decrease in anxiety, muscle relaxation and anticonvulsant effects. 

Knowledge of the interaction of benzodiazepines and the immune system is much less advanced compared to our understanding of interactions between opioid systems and the immune system. It is clear that the benzodiazepines have strong anti-anxiety effects and that through these actions they reduce the response to stressful situations (Zavala, 1997). This, in turn, will reduce stress-induced activation of the HPA axis and so reduce its regulatory effects on the immune system. These effects are centrally mediated, however, and can be considered indirect effects. 

Common adverse events clonidine has a centrally mediated sedative effect. Other CNS depressants, such as benzodiazepines and opioids, may enhance the sedative effects of clonidine. Neuraxial clonidine can also affect the sympathetic nervous system, resulting in hypotension and bradycardia. When clonidine is used as a neuraxial adjunct analgesic, its hemodynamic effects may be enhanced by other neuraxial medications, particularly as local anesthetics. AU effects are dose- dependent. 

The NE system mediates various autonomic, neuroendocrine, emotional and cognitive functions. One of the central roles of NE is response to stress and aversion. This role can be summarized as an activation of response to the acute stress and aversion, followed by decreased reaction to repeated or chronic aversion. Since the response to stress and aversion is a basic part in pathology of mood disorder, NE should play an important role in anxiety, depression and mania. Indeed, this role has been demonstrated in numerous animal and human studies. Majority of antidepressant drugs and mood stabilizers affect NE system as their direct or indirect target. Various medications have different effects on NE neuronal activity. The majority of antidepressants, Li and benzodiazepines suppress NE transmission. Other medications, such as AADs, activate NE neuronal firing activity and NE release. Appropriate combination of different medications, based on the consideration of their effect on NE system, might be critical to obtain good treatment outcome. The combination of SSRIs... 

The toxic and therapeutic effects of this drug have been attributed, in large part, to the potentiation of y-aminobutyric acid (GABA) in the central nervous system (CNS). GABA is a neurotransmitter which mediates pre- and postsynaptic inhibition. Diazepam influences GABA activity by binding to the benzodiazepine receptor complex, thus resulting in increased CNS inhibition. 

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